Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.68613856
A series of analogs of glucagon like peptide 1 ( GLP 1 ) was made replacing each amino acid with L alanine to identify side chain functional groups required for interaction with the GLP 1 receptor . 0.68613856^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.59973416
Less is known about how the glucagon receptor distinguishes between glucagon and GLP 1 . ( 2 ) We analysed chimeric glucagon / GLP 1 peptides for their ability to bind and activate the glucagon receptor , the GLP 1 receptor and chimeric glucagon / GLP 1 receptors . 0.59973416^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
A cDNA for the GLP 1 receptor was isolated by transient expression of a rat pancreatic islet cDNA library into COS cells ; this was followed by binding of radiolabeled GLP 1 and screening by photographic emulsion autoradiography . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The present study examined the internalization and degradation of the GLP 1 receptor complex . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Signal transduction of the GLP 1 receptor cloned from a human insulinoma . ^^^ This study demonstrates the molecular cloning of a cDNA for the GLP 1 receptor from a human insulinoma employing a lambda gt 11 cDNA library . ^^^ The cloned cDNA encoded a seven transmembrane domain protein of 463 amino acids which showed high homology to the GLP 1 receptor in normal human pancreas . ^^^ The understanding of GLP 1 receptor regulation and signal transduction will aid in the discovery of compounds that act as agonists of the GLP 1 receptor for potential use in the treatment of diabetes and will facilitate the understanding of its expression under normal and pathophysiological conditions . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Substitutions in the NH 2 terminal part of the glucagon molecule with the corresponding GLP 1 residues , as for example in [ Ala 2 , Glu 3 ] glucagon and [ Val 10 , Ser 12 ] glucagon , reduced the binding affinity for the glucagon receptor several hundred fold without increasing the affinity for the GLP 1 receptor . ^^^ In contrast , introduction of GLP 1 residues into the far COOH terminal part of the glucagon molecule , e . g . [ Val 27 , Lys 28 , Gly 29 , Arg 30 ] glucagon , had a minimal effect on recognition of the glucagon receptor , but improved the affinity of the analog for the GLP 1 receptor up to 200 fold . ^^^ Similarly , substitutions in especially the far COOH terminal part of the GLP 1 molecule with the corresponding glucagon residues , e . g . des Arg 30 [ Met 27 , Asn 28 , Thr 29 ] GLP 1 , decreased the affinity for the GLP 1 receptor several hundred fold ( IC 50 = 0 . 4 190 nM ) without increasing the affinity for the glucagon receptor . ^^^ Conversely , substitutions in the NH 2 terminal part of the GLP 1 molecule impaired the affinity for the GLP 1 receptor only moderately . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Here we studied agonist induced GLP 1 receptor internalization in receptor transfected Chinese hamster lung fibroblasts using three different approaches . ^^^ Thirdly , continuous exposure of GLP 1 receptor expressing cells to iodinated GLP 1 led to a linear accumulation of peptide degradation products in the medium following a lag time of 20 30 min , indicating a continuous cycling of the receptor between the plasma membrane and endosomal compartments . ^^^ Potassium depletion and hypertonicity inhibited transferrin endocytosis , a process known to occur via coated pit formation , as well as GLP 1 receptor endocytosis . ^^^ Surface re expression following one round of GLP 1 receptor endocytosis occurred with a half time of about 15 min . ^^^ Together our data demonstrate that the GLP 1 receptor is internalized upon agonist binding by a route similar to that taken by single transmembrane segment receptors . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Surprisingly , exendin ( 9 39 ) [ Ex ( 9 39 ) ] , a GLP 1 receptor antagonist , and Ex 4 ( 1 39 ) , a GLP 1 receptor agonist , demonstrated some affinity for the GIP receptor , with 39 % and 21 % displacement of [ 125I ] spGIP , respectively , at 1 microM . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Since glucagon like peptide 1 ( 7 36 ) amide ( 7 37 ) ( GLP 1 ) has been found to be a potent insulinotropic hormone , it has been postulated that glucagon stimulates insulin secretion from islet beta cells through the GLP 1 receptor . ^^^ We therefore examined the effects of a GLP 1 receptor antagonist , exendin ( 9 39 ) amide , on glucagon or GLP 1 stimulated insulin release from isolated perfused rat pancreas . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Since the sensitivity of the endocrine pancreas to regulatory hormones can be influenced by their receptor number , we have examined the regulation of glucagon receptor and GLP 1 receptor messenger RNA ( mRNA ) expression in cultured rat pancreatic islets by various factors , including glucose , cAMP , and glucocorticoids . ^^^ By ribonuclease protection assay we have demonstrated the expression of both glucagon and GLP 1 receptor mRNA in cultured rat islets . ^^^ GLP 1 receptor mRNA levels , on the other hand , were not affected by culturing the islets in low glucose concentrations ; however , a small , but significant , decrease in GLP 1 receptor mRNA levels was detected when islets were cultured in 20 mM glucose . ^^^ GLP 1 receptor mRNA levels remained unchanged under all conditions that altered intracellular cAMP levels . ^^^ Finally , in islets cultured in the presence of 10 nM dexamethasone an approximately 50 % decrease in both glucagon and GLP 1 receptor mRNA expression was observed . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Molecular cloning of a cDNA encoding for the GLP 1 receptor expressed in rat lung . ^^^ This receptor has different biochemical features than the GLP 1 receptor in endocrine pancreas . ^^^ A cDNA library from rat lung in a lambda gt 11 vector was screened with a cDNA probe coding for the rat pancreas GLP 1 receptor . ^^^ Thereby , we found a lung GLP 1 receptor cDNA which shows nearly complete homology to the pancreatic beta cell receptor cDNA . ^^^ Expression of the recombinant lung GLP 1 receptor cDNA in CHO cells displayed a pharmacological profile similar to that seen with cells expressing the beta cell derived cDNA . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
This study uses exendin ( 9 39 ) amide as a GLP 1 receptor antagonist to evaluate the contribution of GLP 1 to the incretin effect . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The discovery of exendin ( 9 39 ) , a GLP 1 receptor antagonist , allowed this to be further investigated . ^^^ The IC 50 for GLP 1 receptor binding , using RIN 5AH beta cell membranes , was found to be 0 . 36 nmol / l for GLP 1 and 3 . 44 nmol / l for exendin ( 9 39 ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The incretin effect of GLP 1 is preserved in patients with Type 2 diabetes mellitus ( NIDDM ) , suggesting that GLP 1 receptor agonist can be used therapeutically in this group of patients . ^^^ To investigate this issue we examined the tissue distribution of GLP 1 receptor using RNAse protection assay in order to avoid the cross reactivities with structurally related receptors and to increase the sensitivity of detection . ^^^ The riboprobe was synthesized from the human pancreatic GLP 1 receptor cDNA and used in hybridization experiments with total RNA isolated from different human tissues . ^^^ In addition to the pancreas , we found expression of GLP 1 receptor mRNA in lung , brain , kidney , stomach and heart . ^^^ Peripheral tissues which are the major sites of glucose turnover , such as liver , skeletal muscle and adipose did not express the pancreatic form of the GLP 1 receptor . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Besides the highly selective GLP 1 receptor , PACAP receptors of types 1 and 2 were present on the cell line and coupled to adenylate cyclase . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Stable expression of the rat GLP 1 receptor in CHO cells : activation and binding characteristics utilizing GLP 1 ( 7 36 ) amide , oxyntomodulin , exendin 4 , and exendin ( 9 39 ) . ^^^ In the present study we stably expressed the rat B cell GLP 1 receptor in CHO cells and studied binding characteristics and receptor activation utilizing the naturally occurring receptor agonist GLP 1 ( 7 36 ) amide ( GLP 1 ) , the proglucagon derived GLP 1 related peptide oxyntomodulin , the GLP 1 receptor agonist exendin 4 , and the specific antagonist exendin ( 9 39 ) . ^^^ This study shows that GLP 1 and exendin 4 are potent agonists at the transfected rat B cell GLP 1 receptor whereas oxyntomodulin is only a weak GLP 1 receptor agonist . ^^^ Furthermore , exendin ( 9 39 ) is a potent GLP 1 receptor antagonist . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Glycosylation of the GLP 1 receptor is a prerequisite for regular receptor function . ^^^ The GLP 1 receptor on RINm5F cells is a glycoprotein with a M ( r ) of 63 , 000 . ^^^ Treatment of the receptor with glycopeptidase F generated a protein with a M ( r ) of 51 , 000 , indicating that the GLP 1 receptor contains N linked glycans . ^^^ Tunicamycin exerted no effect on the GLP 1 receptor mRNA expression . ^^^ Our data show that glycosylation of the GLP 1 receptor is a precondition for regular receptor function . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In addition to the presence of GLP 1 receptor in pancreas we found messenger RNA for this receptor in brain , kidney , heart , fat , skeletal muscle , liver , and intestine . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The GLP 1 receptor is a candidate gene for diabetes mellitus , as mutations may induce the impaired insulin response that is a characteristic feature of NIDDM . ^^^ To study the relationship between the GLP 1 receptor gene and NIDDM , linkage of a microsatellite polymorphism flanking the GLP 1 receptor gene with diabetes was investigated in three Caucasian families with MODY and in the nuclear families of 12 NIDDM probands . ^^^ Mutations in or near the GLP 1 receptor gene are unlikely to be the major cause of the inherited predisposition to NIDDM in Caucasian pedigrees , but we can not exclude a role for this locus in a polygenic model or a major role in some pedigrees . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Using these markers , role of GLP 1 receptor mutations in the pathogenesis of NIDDM was studied . ^^^ Linkage was rejected between the GLP 1 receptor gene and NIDDM in Caucasian late onset NIDDM families and in French MODY families . ^^^ Mutations in the GLP 1 receptor gene do not appear to be major genetic determinants of NIDDM . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Ligand specificity of the rat GLP 1 receptor recombinantly expressed in Chinese hamster ovary ( CHO ) cells . ^^^ This study was designed to precisely characterize the binding behavior and activation of the recombinant GLP 1 receptor against naturally occurring ligands of the glucagon / VIP / secretin peptide hormone family . ^^^ CHO cells were stably transfected with a plasmid containing a cDNA encoding for the rat GLP 1 receptor . ^^^ This data shows that the GLP 1 receptor is characterized by a high ligand specificity . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The molecular weight of this apparent GLP 1 receptor in human endocrine pancreatic tissue was of identical size as the GLP 1 receptor on rat insulinoma derived RINm5F cell membranes . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
It is proposed that at least one factor contributing to the pathogenesis of NIDDM is a desensitization of the GLP 1 receptor on beta cells induced by the hypersecretion of GLP 1 . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In contrast , mRNA transcripts for the GLP 1 receptor were detected in both small and large intestine as well as in pancreas , liver , lung , and kidney . ^^^ Both glucagon and GLP 1 receptor mRNA transcripts were identified in different regions of the fetal and adult mouse brain , but the relative levels of GLP 1 receptor mRNA transcripts were much greater in the central nervous system . ^^^ Furthermore , regulation of the GLP 1 receptor ( but not the glucagon receptor ) gene in the brain resembled the pattern of region specific gene expression recently defined for the mouse proglucagon gene . ^^^ Taken together , these studies define novel sites for both glucagon and GLP 1 receptor gene expression in the mouse and suggest that different regulatory mechanisms have evolved for tissue specific and developmental control of receptor gene expression . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Here we studied the coupling of the cloned GLP 1 receptor , expressed in fibroblasts or in COS cells , to intracellular second messengers and compared this signaling with that of the endogenous receptor expressed in insulinoma cell lines . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The hypothesis to be tested in this study was that defects in the islet beta cell GLP 1 receptor gene contribute to the impaired glucose regulated insulin secretion of non insulin dependent diabetes mellitus ( NIDDM ) . ^^^ Human islet GLP 1 receptor genomic clones were isolated , and two highly polymorphic simple sequence repeat regions ( GLP 1R CA 1 and GLP 1R CA 3 ) were identified . ^^^ By genotyping all members of the 40 reference Centre d ' Etude du Polymorphisme Humain pedigrees at GLP 1R CA 3 , the human GLP 1 receptor gene was uniquely placed on chromosome 6p between GLO 1 and D6S19 , 20 . 4 cM from human leukocyte antigen . ^^^ To assess the possible role of the GLP 1 receptor gene in determining the genetic susceptibility to NIDDM , allelic frequencies of GLP 1R CA 1 and GLP 1R CA 3 were compared between African American NIDDM patients ( n = 95 ) and control subjects ( n = 93 ) . ^^^ The GLP 1 receptor gene simple sequence repeat polymorphisms were used for linkage analysis in Utah Mormon pedigrees ( n = 16 ) with NIDDM . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Transfection of the human GLP 1 receptor into COS 7 cells confers upon them high affinity binding for [ 125I ] GLP 1 ( 7 36 ) amide . ^^^ In membranes prepared from COS 7 cells transfected with the human GLP 1 receptor , the binding of [ 125I ] GLP 1 ( 7 36 ) amide is inhibited with the rank order of potency GLP 1 ( 7 36 ) amide > glucagon > secretin , characteristic of a GLP 1 receptor . ^^^ The human GLP 1 receptor is functionally coupled to increases in intracellular cAMP in these cells : incubation of COS 7 cells expressing the human GLP 1 receptor with GLP 1 ( 7 36 ) amide gives rise to a 4 fold increase in cyclic AMP over basal levels , with an EC 50 of 25pM . ^^^ Glucagon is also a full agonist but is 200 fold less potent than GLP 1 ( 7 36 ) amide in stimulating the human GLP 1 receptor . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Isolation and sequencing of cDNA of the GLP 1 receptor ] . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
This study establishes that a single GLP 1 receptor species can mediate the effects of GLP 1 ( 7 37 ) through multiple G protein coupled signaling pathways , including the adenylyl cyclase system , phospholipase C , and changes in [ Ca2+ ] i . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The biological actions of GLP 1 are mediated by the GLP 1 receptor , the structure of which has recently been determined . ^^^ Defects in insulin secretion are a common feature of NIDDM and as such the GLP 1 receptor is a candidate for contributing to the development of this clinically and genetically heterogeneous disorder . ^^^ As a first step in determining the role of the GLP 1 receptor in the development of NIDDM , we have isolated the human GLP 1 receptor gene and mapped it to chromosome 6 , band p21 . 1 , using the technique of fluorescence in situ hybridization . ^^^ We also identified a simple tandem repeat DNA polymorphism in the human GLP 1 receptor gene of the form ( TG ) n . ^^^ We have used this DNA polymorphism to localize the GLP 1 receptor gene within the genetic map of the short arm of chromosome 6 . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
We demonstrate that exendin 4 and truncated exendin ( 9 39 ) amide specifically interact with the GLP 1 receptor on insulinoma derived cells and on lung membranes . ^^^ In conclusion , exendin 4 is an agonist and exendin ( 9 39 ) amide is a specific GLP 1 receptor antagonist . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
To determine the structure and coupling mechanisms of the human GLP 1 receptor we have isolated two pancreatic islet cDNAs , encoding the 463 amino acid receptor and differing mainly in their 3 ' untranslated regions . ^^^ The deduced amino acid sequence is 90 % homologous with the rat GLP 1 receptor . ^^^ Thus , like the structurally related glucagon and parathyroid hormone receptors , the human GLP 1 receptor can activate multiple intracellular signaling pathways including adenylyl cyclase and PLC . ^^^ Knowledge of the GLP 1 receptor structure will facilitate the development of receptor agonists and elucidation of the important role of GLP 1 in normal physiology and disease states . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Cloning and functional expression of the human islet GLP 1 receptor . ^^^ Two peptides from the venom of the lizard Heloderma suspectum , exendin 4 and exendin ( 9 39 ) , displayed similar ligand binding affinities to the human GLP 1 receptor . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Binding studies with [ 125I ] [ Tyr 39 ] exendin 4 , a GLP 1 receptor agonist , showed an identical distribution pattern of binding sites . ^^^ In conclusion , the biochemical data support the idea that the central GLP 1 receptor resembles the peripheral GLP 1 receptor . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
By Northern blot analysis the presence of GLP 1 receptor mRNA was shown in B ( beta TC 1 cells ) and D ( RIN 1048 38 ) cells but not in A ( INR 1 G9 ) cells , thus confirming functional data demonstrating the absence of active GLP 1 receptors on glucagon producing cells . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
A series of chimeric receptors in which 4 6 amino acids in the N terminal extracellular domain of the human GLP 1 receptor were replaced with the analogous region of the human glucagon receptor were constructed and expressed in COS 7 cells . ^^^ Thus , the substitution of as few as four residues of the GLP 1 receptor profoundly affects its selectivity for the homologous peptide agonists GLP 1 and glucagon . ^^^ These results suggest the extracellular N terminal domain of the GLP 1 receptor harbours molecular determinants for both agonist binding affinity and selectivity . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In this study , we examined the tissue distribution of GLP 1 receptor ( GLP lR ) messenger RNA ( mRNA ) in rat by RNAse protection , RT PCR , and in situ hybridization . ^^^ These results indicate that sequences corresponding to the cloned rat islet GLP 1 receptor are expressed in the pancreatic islets , lung , hypothalamus , stomach , heart , and kidney but not in adipose , liver , and skeletal muscle . ^^^ Further , the GLP 1 receptor expressed in the kidney and heart may be structural variants of the known receptor . ^^^ Therefore , the observed extrapancreatic actions of GLP 1 may not be strictly confined to interactions with the defined GLP 1 receptor . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The binding affinity to the GLP 1 receptor was found to be sensitive to GIP like exchanges in the N terminal 22 amino acids as well as in positions 13 and 15 ( loss of affinity 280 fold to more than 1000 fold ) . ^^^ C terminal substitution of the GLP 1 sequence by GIP diminished the affinity towards the GLP 1 receptor only 20 fold . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Exchange of W 39 by A within the N terminal extracellular domain of the GLP 1 receptor results in a loss of receptor function . ^^^ The GLP 1 receptor belongs to a new subfamily of the superfamily of seven transmembrane , G protein coupled receptors ( 7 TM receptors ) . ^^^ We show that a single point mutation within a nonconserved motif of the N terminal , extracellular domain of the GLP 1 receptor results in a dramatic impairment of receptor function . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Down regulation of the GLP 1 receptor mRNA was observed after exposure of CA 77 C cells with GLP 1 ( 7 37 ) . ^^^ GLP 1 ( 7 37 ) increased cAMP formation in CA 77 cells in a dose dependent manner ; exendin ( 9 39 ) , a GLP 1 receptor antagonist , inhibited cAMP production . ^^^ The GLP 1 peptide which is produced by intestinal cells could be involved in the control of CT secretion through an entero thyroidal axis implying GLP 1 receptor and increased CT gene expression . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The specific GLP 1 receptor agonists , exendin 4 and exendin 3 , and the antagonist , exendin ( 9 39 ) , bound to the receptor sites with high affinity ( Ki = 190 + / 70 pM ; 130 + / 50 and 1200 + / 470 pM , respectively ) . ^^^ Chemical cross linking of [ 125I ] GLP 1 receptor complexes revealed a single band of 64 , 300 + / 100 Mr in alpha TSH membranes . ^^^ In addition , specific PCR studies demonstrated the presence of GLP 1 receptor messenger RNA . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Internalization of the GLP 1 receptor did not participate in the desensitization induced by PMA , as a mutant GLP 1 receptor lacking the last 20 amino acids of the cytoplasmic tail was found to be totally resistant to the internalization process , but was still desensitized after PMA preexposure . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Colocalization of glucagon like peptide 1 ( GLP 1 ) receptors , glucose transporter GLUT 2 , and glucokinase mRNAs in rat hypothalamic cells : evidence for a role of GLP 1 receptor agonists as an inhibitory signal for food and water intake . ^^^ This hypothesis was confirmed by analyzing the effects of both systemic and central administration of GLP 1 receptor ligands . ^^^ Pretreatment with an i . c . v . dose of a GLP 1 receptor antagonist [ exendin ( 9 39 ) ; 2 , 500 ng ] reversed the inhibitory effects of GLP 1 ( 7 36 ) amide ( 1 , 000 ng dose ) and exendin 4 ( 25 ng dose ) on food and water ingestion . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The GLP 1 receptor belongs to the family of seven transmembrane domain receptors coupled to G proteins . ^^^ We have analyzed the regulation of GLP 1 receptor function and expression by its own ligand and the cAMP dependent pathway in rat insulinoma derived beta cells ( RINm5F ) . ^^^ The GLP 1 receptor underwent rapid homologous desensitization , which occurred at the receptor level . ^^^ GLP 1 receptor mRNA levels were down regulated during incubation of cells by agents increasing cAMP levels including GLP 1 itself . ^^^ Forskolin , the PKA activator 5 , 6 dichloro 1 beta D ribofuranosyl benzimidazole 3 , 5 monophosphorothiotate , and GLP 1 stabilized the GLP 1 receptor mRNA . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Glucagon like peptide 1 receptor ( GLP 1 R ) mRNA in the rat hypothalamus . ^^^ To date , little is known about the distribution of GLP 1 R and its mRNA in the rodent hypothalamus . ^^^ The purpose of the present study was to utilize in situ hybridization histochemistry to determine the anatomical distribution of GLP 1 R mRNA in the rat hypothalamus . ^^^ The results of these studies revealed an extensive distribution of GLP 1 R mRNA throughout the rostral caudal extent of the hypothalamus ; with a dense accumulation of labeled cells in the supraoptic , paraventricular , and arcuate nuclei . ^^^ The results of these in situ hybridization histochemical studies have provided detailed and novel information about the distribution of GLP 1 R mRNA in the rat hypothalamus . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
To ascertain the relative physiological importance of GLP 1 as a regulator of feeding behavior and insulin secretion , we have generated mice with a targeted disruption of the GLP 1 receptor gene ( GLP1R ) . ^^^ Intracerebroventricular administration of GLP 1 inhibited feeding in wild type mice but not in GLP1R / mice ; however , no evidence for abnormal body weight or feeding behavior was observed in GLP1R / mice . ^^^ These observations demonstrate that GLP 1 plays a central role in the regulation of glycemia ; however , disruption of GLP1 / GLP1R signaling in the central nervous system is not associated with perturbation of feeding behavior or obesity in vivo . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The GLP 1 receptor belongs to the family of seven transmembrane domain receptors . ^^^ TPA induced significantly lower GLP 1 receptor mRNA levels under steady state conditions after 6 and 24 h . ^^^ The stability of the GLP 1 receptor mRNA was unchanged . ^^^ These data indicate that PKC activation downregulates the expression of the GLP 1 receptor gene , mainly at the transcriptional level . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
It is , however , unknown whether oxyntomodulin and GLP 2 elicit a biological response by interacting with the GLP 1 receptor . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The GLP 1 receptor is presently attracting much attention , since it is the target protein of the antidiabetic gut hormone GLP 1 . ^^^ To establish the functional significance of the N terminal part of the GLP 1 receptor for ligand binding , the extracellular domain was isolated and purified . ^^^ Utilizing CHL cells expressing the cloned GLP 1 receptor , we demonstrate that the isolated , solubilized N terminal part of the receptor protein competes for GLP 1 binding with the intact wild type receptor . ^^^ These data underline the significance of the N terminal domain of the GLP 1 receptor for ligand binding . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
ICV injection of the specific GLP 1 receptor antagonist , exendin ( 9 39 ) , blocked the inhibitory effect of GLP 1 on food intake . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Roles of the RAM and ANK domains in signaling by the C . elegans GLP 1 receptor . ^^^ In Caenorhabditis elegans , the GLP 1 receptor acts with a downstream transcriptional regulator , LAG 1 , to mediate intercellular signaling . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Receptor binding studies using baby hamster kidney cells expressing the human pancreatic GLP 1 receptor showed that the affinity of GLP 1 ( 9 36 ) amide , GLP 1 ( 7 35 ) and GLP 1 ( 7 34 ) was 0 . 95 % , 12 % and 2 . 8 % , respectively , of the affinity of GLP 1 ( 7 36 ) amide . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
A lizard glucagon like peptide 1 ( GLP 1 ) related peptide , exendin 4 , binds to the GLP 1 receptor and mimics the actions of GLP 1 in vivo . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Reciprocal cellular distribution of glucagon like peptide 1 ( GLP 1 ) immunoreactivity and GLP 1 receptor mRNA in pancreatic islets of rat . ^^^ The respective cellular distribution of glucagon like peptide 1 ( GLP 1 ) immunoreactivity and mRNA expression of the GLP 1 receptor was compared in rat pancreas by means of immunohistochemistry and in situ hybridization . ^^^ In contrast , GLP 1 receptor mRNA signals were confined to the central part of pancreatic islets . ^^^ Neither GLP 1 immunoreactivity nor GLP 1 receptor mRNA signals were detected in the exocrine pancreatic acinar cells or duct cells . ^^^ The differential distribution of GLP 1 immunoreactivity and GLP 1 receptor mRNA signals indicates that the GLP 1 amino acid sequence is present in the alpha cell zone of pancreatic islets , whereas the GLP 1 receptor is expressed mainly by beta cells . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In contrast , expression of GLP 1 receptor gene was detected in brain , pancreas and pancreatic islets but not in liver , kidney , or ileum . ^^^ In the cDNA pool of MIN 6 cells , both glucagon and GLP 1 receptor genes were identified and showed higher expression level in MIN 6 cells cultured under high glucose condition than in those cultured under low glucose condition . ^^^ These results suggest that glucagon and GLP 1 receptor genes are expressed in pancreatic beta cells and their expression is upregulated by glucose . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The localization of the GLP 1 receptor on insulin and somatostatin producing cells in the islets is well established . ^^^ Whether the GLP 1 receptor also resides on the glucagon producing alpha cells remains controversial and is reported to be absent on rat alpha cells . ^^^ To investigate the distribution of the GLP 1 receptor on islet cells , we examined the expression of GLP 1 receptor mRNA in phenotypically distinct islet cell lines and islets , and the presence of immunoreactive GLP 1 receptor in dispersed rat islet cells using a specific antiserum . ^^^ GLP 1 receptor mRNA was readily detected by reverse transcription polymerase chain reaction ( RT PCR ) in both rat islets and in established islet cell lines representing distinct alpha , beta , and delta cell phenotypes . ^^^ In addition , GLP 1 receptor expression was detected in single rat alpha cells by single cell RT PCR . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Five out of six tryptophan residues in the N terminal extracellular domain of the rat GLP 1 receptor are essential for its ability to bind GLP 1 . ^^^ This indicates the significance of hydrophobic interactions within the N terminal domain of the GLP 1 receptor . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Fluorescein Trp 25 exendin 4 , a biologically active fluorescent probe for the human GLP 1 receptor . ^^^ FLEX is equipotent to GLP 1 ( 7 36 ) amide and exendin 4 as an inhibitor of [ 125I ] GLP 1 binding to the human GLP 1 receptor stably expressed in CHO cells , and maintains full biological potency and efficacy as measured by the stimulation of cAMP accumulation in these cells . ^^^ The binding is specific and saturable ( Kd = 2 . 0 + / 0 . 4 nM ) , and GLP 1 ( 7 36 ) amide and exendin 4 are equipotent inhibitors of FLEX binding to the human GLP 1 receptor . ^^^ Thus , FLEX is a potent , biologically active ligand that is useful for the study of the binding and functional characteristics of the human GLP 1 receptor . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Internalization and homologous desensitization of the GLP 1 receptor depend on phosphorylation of the receptor carboxyl tail at the same three sites . ^^^ Homologous desensitization and internalization of the GLP 1 receptor correlate with phosphorylation of the receptor in a 33 amino acid segment of the cytoplasmic tail . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Cloning and characterization of the 5 ' flanking sequences ( promoter region ) of the human GLP 1 receptor gene . ^^^ To elucidate the tissue specific regulation of the GLP 1 receptor we screened a human genomic library with a human GLP 1 receptor cDNA . ^^^ Transient transfections of GLP 1 receptor producing and non producing cells with promoter / reporter gene constructs revealed that the putative Sp 1 binding sites and several other silencer and tissue specific elements are important for the activity . ^^^ Therefore , 3000 bp upstream the GLP 1 receptor coding sequences comprise regulatory elements essential for the tissue and cell specific transcription of the gene . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In this study , we evaluated the effects of stably transfecting the GLP 1 receptor into an insulinoma cell line , RIN 1046 38 , on basal and glucose mediated insulin secretion and on second messenger pathways involved in insulin secretion . ^^^ The GLP 1 receptor transfected cells had similar insulin mRNA levels but higher insulin content compared with parental cells . ^^^ In GLP 1 receptor transfected cells , glucose ( 0 . 5 mM ) mediated insulin release was increased compared with parental cells ( 4 . 52 + / 0 . 79 pmol insulin / l per mg protein 10 h vs . 2 . 21 + / 0 . 36 pmol insulin / l per mg protein 10 h ; mean + / S . ^^^ By hemolytic plaque assay measuring single cell insulin secretion , we observed that in the GLP 1 receptor transfected cells versus parental cells the increased insulin secretion was due to the presence of more glucose responsive cells as well as more insulin released in response to glucose per cell . ^^^ In response to GLP 1 , both GLP 1 receptor transfected cells and parental cells showed increased cAMP levels independent of glucose . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Unexpectedly , these cDNAs were found to encode three unique glucagon like 1 peptides , termed xenGLP 1A , xenGLP 1B , and xenGLP 1C in addition to the typical proglucagon derived hormones glucagon and GLP 2 . xenGLP 1A , 1B , and 1C were synthesized and tested for their ability to bind and activate the human GLP 1 receptor ( hGLP 1R ) , and to stimulate insulin release from rat pancreas . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The stimulatory action of GLP 1 ( 7 36 ) amide on exocytosis was mimicked by the pancreatic hormone glucagon and exendin 4 , a GLP 1 receptor agonist . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
To analyze the transition from agonist to antagonist and to identify the amino acid residues involved in ligand activation of the GLP 1 receptor , we used exendin analogs with successive N terminal truncations . ^^^ Chinese hamster ovary cells stably transfected with the rat GLP 1 receptor were assayed for changes in intracellular cAMP caused by the test peptides in the absence or presence of half maximal stimulatory doses of GLP 1 . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In addition , an antagonist of pancreatic GLP 1 receptor , exendin 4 ( 9 39 ) , acted as an agonist to decrease cAMP levels in 3T3 L 1 adipocytes as did exendin 4 ( 1 39 ) , a known agonist for the pancreatic GLP 1 receptor . ^^^ Binding studies using 125I GLP 1 also suggest that pancreatic GLP 1 receptor isoform is not responsible for the effect of GLP 1 and related peptides in 3T3 L 1 adipocytes . ^^^ Based on these results , we propose that the major form of the GLP receptor in 3T3 L 1 adipocytes is functionally different from the pancreatic GLP 1 receptor . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
ICV injection of the specific GLP 1 receptor antagonist , exendin ( 9 39 ) , at the onset of dark phase , did not affect feeding in saline pre treated controls , but blocked the reduction in food intake and body weight of leptin pre treated rats . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In gastric fistula rats , vagal afferent denervation and peripheral administration of the GLP 1 receptor antagonist exendin ( 9 39 ) amide enhanced emptying of a glucose meal , whereas intracerebroventricular exendin was ineffective . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
GLP 1 receptor gen `` knock out ' ' causes glucose intolerance , but no alterations of eating behavior ] . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Because leptin reduces food intake but inhibits insulin secretion , we examined leptin action in mice with a null mutation in the GLP 1 receptor . ^^^ Intracerebroventricular leptin administration inhibited food intake in both wild type and GLP 1 receptor ( GLP IR ) / mice , and daily intraperitoneal administration of leptin for 2 weeks produced comparable reductions in food intake and body weight in control and GLP IR / mice . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
It is proposed that at least one factor contributing to the pathogenesis of non insulin dependent diabetes mellitus ( NIDDM ) is desensitization of the GLP 1 receptor on beta cells . ^^^ Agonists of GLP 1 receptor have been proposed as new potential therapeutic agents in NIDDM patients . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Glucagon induced cAMP production in beta cells was inhibited both by 1 micromol / l des His 1 [ Glu 9 ] glucagon amide and exendin ( 9 39 ) amide , a specific GLP 1 receptor antagonist , whereas GLP 1 induced cAMP formation was suppressed only by exendin ( 9 39 ) amide . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
This inhibitory action occurs independent of circulating concentrations of somatostatin and gastrin and appears to involve a GLP 1 receptor distinct from that mediating incretin effects . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
GLP 1 receptor binding and GLP 1 induced cAMP generation remained unchanged . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The specific GLP 1 receptor agonists , exendin 3 and exendin 4 , also showed high affinity ( Ki = 0 . 3+ / 0 . 05 and 0 . 32+ / 0 . 06 nM , respectively ) as did the antagonist exendin ( 9 39 ) ( Ki = 0 . 98+ / 0 . 24 nM ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In vitro functional densensitization of the GLP 1 receptor was not observed after overnight exposure of Rin m5F insulinoma cells to GLP 1 at concentrations up to 10 nM . ^^^ These results indicate that the GLP 1 pathways in the central nervous system controlling food consumption do not desensitize after chronic exposure to GLP 1 and suggest that agonists of the central GLP 1 receptor may be effective agents for the treatment of obesity . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
We conclude that GLP 1 receptor expression in Xenopus oocytes evokes inositol trisphosphate dependent intracellular Ca2+ mobilization independent of the cAMP / PKA signaling pathway . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
We demonstrate here a gene dosage effect for the incretin action of GLP 1 , as heterozygous GLP 1R + / mice exhibit an abnormal glycemic response to oral glucose challenge in association with reduced circulating levels of glucose stimulated insulin . ^^^ In contrast , GLP 1 signaling is not required for normal control of fasting and postabsorptive glucagon levels , and no significant changes were detected in the tissue content of pancreatic and intestinal proglucagon mRNA , glucagon like immunoreactivity , or GLP 1 in GLP 1R / or + / mice . ^^^ Despite the demonstration that GLP 1 stimulates proinsulin gene transcription , pancreatic insulin mRNA transcripts were similar in wild type and GLP 1R / mice . ^^^ Furthermore , despite suggestions that GLP 1 regulates peripheral glucose disposal , whole body glucose utilization was similar in wild type and GLP 1R / mice under both basal and hyperinsulinemic conditions . ^^^ Identification of glucagon like peptide 1 ( GLP 1 ) actions essential for glucose homeostasis in mice with disruption of GLP 1 receptor signaling . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The observation that mice with homozygous disruption of the GLP 1 receptor gene are diabetic with a diminished incretin response to glucose underlines the first function in vivo . ^^^ Isolated islets of Langerhans from GLP 1 receptor / mice were studied to assess the second function in vitro . ^^^ Absence of pancreatic GLP 1 receptor function was observed in GLP 1 receptor / mice , as exemplified by loss of [ 125I ] GLP 1 binding to pancreatic islets in situ and by the lack of GLP 1 potentiation of glucose induced insulin secretion from perifused islets . ^^^ Acute glucose competence of the beta cells , assessed by perifusing islets with stepwise increases of the medium glucose concentration , was well preserved in GLP 1 receptor / islets in terms of insulin secretion . ^^^ Furthermore , neither islet nor total pancreatic insulin content was significantly changed in the GLP 1 receptor / mice when compared with age and sex matched controls . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
It plays an important role as an incretin hormone ; thus , mice with a null muation in the gene encoding the GLP 1 receptor are glucose intolerant . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Despite the inhibitory effects of GLP 1 on food intake , 6 to 8 week old GLP 1 receptor / ( GLP 1R / ) mice were not obese and did not exhibit disturbances of feeding behavior . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Despite the physiological importance of the enteroinsular axis , disruption of glucagon like peptide ( GLP ) 1 action is associated with only modest glucose intolerance in GLP 1 receptor / ( GLP 1R / ) mice . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Inhibition induced by GLP 1 was reversed by i . v . infusion of GLP 1 receptor antagonist , Exendin ( 9 39 ) ( 3 10 10 ( 8 ) moles / kg per 10 min ) ( n = 6 ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In conclusion , GLP 1 seems to inhibit small bowel motility directly via the GLP 1 receptor . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Tissue distribution of rat glucagon receptor and GLP 1 receptor gene expression . ^^^ This paper highlights the diversity of both GLP 1 and glucagon activity by studying the tissue distribution of glucagon and GLP 1 receptor gene expression by both Southern blot analysis of RT PCR products and nuclease protection assays . ^^^ By Southern blot analysis of RT PCR products , GLP 1 receptor mRNA was detected in lung , hypothalamus , hippocampus , cerebral cortex , kidney , pancreas , and throughout the gastrointestinal tract . ^^^ Nuclease protection assay revealed glucagon receptor expression to be highest in liver and kidney , whereas GLP 1 receptor expression was only detected by protection assay in lung , stomach , and large bowel . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
We therefore determined if third ventricular ( i3vt ) infusion of a GLP 1 receptor antagonist would block LiCl induced c Fos expression in the brainstem . ^^^ Relative to rats pretreated with i3vt infusion of vehicle , pretreatment with the potent GLP 1 receptor antagonist , des His 1 Glu9 exendin 4 ( 10 . 0 microgram ) , significantly attenuated LiCl induced ( 76 mg / kg ; i . p . ) c Fos expression in several brainstem regions , including the area postrema , the nucleus of the solitary tract , and the lateral parabrachial nucleus . ^^^ These results suggest that LiCl induced c Fos expression in the rat brainstem is mediated , at least in part , by GLP 1 receptor signaling . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
GLP 1 action in L 6 myotubes is via a receptor different from the pancreatic GLP 1 receptor . ^^^ The incretin hormone glucagon like peptide 1 ( GLP 1 ) ( 7 36 ) amide is best known for its antidiabetogenic actions mediated via a GLP 1 receptor present on pancreatic endocrine cells . ^^^ In L 6 myotubes transfected with pancreatic GLP 1 receptor , GLP 1 increased cAMP levels and inhibited glycogen synthesis by 60 % . ^^^ An antagonist of pancreatic GLP 1 receptor , exendin 4 ( 9 39 ) , inhibited GLP 1 mediated glycogen synthesis in GLP 1 receptor transfected L 6 myotubes . ^^^ However , in parental L 6 myotubes , exendin 4 ( 9 39 ) and GLP 1 ( 1 36 ) amide , an inactive peptide on pancreatic GLP 1 receptor , displaced 125I labeled GLP 1 binding and stimulated glycogen synthesis by 186 and 130 % , respectively . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In Northern blots , transcripts of 2 . 7 , 3 . 6 and 3 . 7 kb were observed in rat islets and RINm5F cells after hybridization with rat GLP 1 receptor cDNA probes of either 21 9 bp or 1 . 5 kb . ^^^ However , a single 3 . 6 kb transcript was observed in the latter two cases when a human GLP 1 receptor cDNA probe of 1 . 6 kb was used for hybridization . ^^^ The expression of the mRNA for the GLP 1 receptor differs , however , from that found in rat or human islets . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The GLP 1 receptor ( GLP 1R ) mediates the insulinotropic effects of the incretion hormone glucagon like peptide 1 ( 7 36 ) amide ( GLP 1 ) . ^^^ Contribution of a PS 1 like element to the tissue and cell specific expression of the human GLP 1 receptor gene . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
High level expression of the GLP 1 receptor results in receptor desensitization . ^^^ The GLP 1 receptor is desensitized when expressed in high numbers on the cells . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The genomic organization of the human GLP 1 receptor gene . ^^^ The coding sequence of the GLP 1 receptor is interrupted by 12 introns . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The insulinotropic hormone , glucagon like peptide 1 ( GLP 1 ) , which has been proposed as a new treatment for type 2 diabetes , is metabolized extremely rapidly by the ubiquitous enzyme , dipeptidyl peptidase 4 ( DPP 4 ) , resulting in the formation of a metabolite , which may act as an antagonist at the GLP 1 receptor . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
This latter effect was receptor dependent , as a beta cell line not expressing the GLP 1 receptor was not affected by exendin ( 9 39 ) . ^^^ These data therefore demonstrated that 1 ) exendin ( 9 39 ) is an inverse agonist of the murine GLP 1 receptor ; 2 ) the decreased basal cAMP levels induced by this peptide inhibit the secretory response of betaTC Tet cells and mouse pancreatic islets to glucose ; 3 ) as this effect was observed only with growth arrested cells , this indicates that the mechanism by which cAMP leads to potentiation of insulin secretion is different in proliferating and growth arrested cells ; and 4 ) the presence of the GLP 1 receptor , even in the absence of bound peptide , is important for maintaining elevated intracellular cAMP levels and , therefore , the glucose competence of the beta cells . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Using glucose responsive HIT T 15 cells , [ Ser ] GLP 1 ( 7 36 ) amide showed strong insulinotropic activity , which was inhibited by the specific GLP 1 receptor antagonist exendin 4 ( 9 39 ) amide . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Glucagon like peptide 1 ( GLP 1 ) is derived from the peptide precursor pre pro glucagon ( PPG ) by enzymatic cleavage and acts via its receptor , glucagon like peptide 1 receptor ( GLP 1R ) . ^^^ These studies , in addition to describing the sites of GLP 1 and GLP 1R synthesis , suggest that the efferent connections from the nucleus of the solitary tract are more widespread than previously reported . ^^^ The widespread distribution of GLP 1R mRNA containing cells strongly suggests that GLP 1 not only functions as a satiety factor but also acts as a neurotransmitter or neuromodulator in anatomically and functionally distinct areas of the central nervous system . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In situ hybridization histochemistry revealed colocalization of the mRNAs for GLP 1 receptor , AVP , and OX in neurons of the hypothalamic supraoptic and paraventricular nuclei . ^^^ The coexpression of GLP 1 receptor and AVP mRNAs in hypothalamic supraoptic and paraventricular nuclei gives further support to the already reported central effects of GLP 1 ( 7 36 ) amide on AVP . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
We here report that repeated intracerebroventricular ( i . c . v . ) injection of GLP 1 or the GLP 1 receptor antagonist , exendin ( 9 39 ) , affects food intake and body weight . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Recently , we cloned the 5 ' region of the GLP 1 receptor gene and found that tissue and cell specificity is lost by 5 ' deletion to 574 . ^^^ Therefore , the basal activity of the GLP 1 receptor gene is mediated by two proximal Sp 1 binding sites , whereas a more distal site acts as a repressor . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Duodenal inhibition induced by intraduodenal ( N = 6 ) or intraileal ( N = 6 ) infusion of ovoalbumin hydrolysate was reversed by intraarterial infusion of GLP 1 receptor antagonist , exendin ( 9 39 ) ( 3 10 10 ( 8 ) mol / kg / 40 min ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Also , GLP 1 receptor cDNA from human and rat brains has been cloned and sequenced , and the deduced amino acid sequences are the same as those found in pancreatic islets . ^^^ Central administration ( icv ) of GLP 1 ( 7 36 ) amide produces a marked reduction in food and water intake , and the colocalization of the GLP 1 receptor , GLUT 2 , and glucokinase mRNAs in hypothalamic neurons involved in glucose sensing suggests that these cells may be involved in the transduction of signals needed to produce a state of fullness . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Chinese hamster ovary ( CHO ) cells stably expressing the human insulin receptor and the rat glucagon like peptide 1 ( GLP 1 ) receptor ( CHO / GLPR ) were used to study the functional coupling of the GLP 1 receptor with G proteins and to examine the regulation of the mitogen activated protein ( MAP ) kinase signaling pathway by GLP 1 . ^^^ We showed that ligand activation of GLP 1 receptor led to increased incorporation of GTP azidoanilide into Gs alpha , Gq / 11 alpha , and Gi 1 , 2 alpha , but not Gi 3 alpha . ^^^ Ligand stimulated GLP 1 receptor produced 1 . 45 and 2 . 7 fold increases in tyrosine phosphorylation of 42 kDa extracellular signal regulated kinase ( ERK ) in CHO / GLPR and RIN 1046 38 cells , respectively . ^^^ Our study indicates a direct coupling between the GLP 1 receptor and several G proteins , and that CTX sensitive proteins are required for GLP 1 mediated activation of MAP kinases . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
GLP 1 receptor binding was investigated in RINm5F cells . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Genes that have been shown to have a regulatory function in the control of body fat utilization , eating behavior , and / or metabolic rate in rodent models of obesity include leptin ( LEP ) , leptin receptor ( LEPR ) , neuropeptide Y ( NPY ) , NPY Y 1 receptor ( NPYY 1 ) , glucagon like peptide 1 ( GLP 1 ) , GLP 1 receptor ( GLP1R ) , and uncoupling protein 1 ( UCP 1 ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
This effect is reproduced by 8 Br cAMP , but is blocked by a GLP 1 receptor antagonist ( exendin ( 9 39 ) ) , a cAMP antagonist ( ( Rp ) cAMPS ) , an L type Ca2+ channel antagonist ( nimodipine ) , an antagonist of the sarco ( endo ) plasmic reticulum Ca2+ ATPase ( thapsigargin ) , or by ryanodine . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
GLP 1 receptor gene expression was found using reverse transcriptase polymerase chain reaction of poly ( A ) selected RNA in muscle and adipose tissue , but not in liver . ^^^ Low levels of GLP 1 receptor gene expression were also found in adipose tissue using Northern blotting . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
TPRA 40 has seven putative transmembrane domains and shows little homology with the known GLP 1 receptor or with other G protein coupled receptors . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Using a peptide analog of GLP 1 , the GLP 1 receptor antagonist exendin ( 9 39 ) , we investigated whether the conjugation of a carbohydrate structure to exendin ( 9 39 ) would generate a peptide with intact biological activity and improved survival in circulation . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Structure of the integral membrane domain of the GLP 1 receptor . ^^^ A three dimensional ( 3D ) model of the integral membrane domain of the GLP 1 receptor , a member of the secretin receptor family of the G protein coupled receptor superfamily is proposed . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Recently , we generated two GLP 1 receptor mutant isoforms ( IC 3 1 and DM 1 ) that displayed efficient ligand binding and the ability to promote Ca2+ mobilization from intracellular stores but lacked the ability to couple to AC . ^^^ In the present study , the wild type rat GLP 1 receptor ( WT GLP 1 R ) or the IC 3 1 and DM 1 mutant forms were expressed for the first time in the insulin producing HIT T 15 cells . ^^^ These studies demonstrate that the GLP 1 receptor efficiently couples to AC to stimulate insulin secretion and that receptors lacking critical residues in the proximal region of the third intracellular loop can effectively uncouple the receptor from cAMP production , VDCC activity , insulin secretion , and insulin biosynthesis . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
A GLP 1 receptor antagonist or GLP 1 antisera have been shown to reduce meal stimulated insulin secretion in animals , suggesting that GLP 1 has a physiological `` incretin ' ' function ( augmentation of postprandial insulin secretion due to intestinal hormones ) for GLP 1 . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Juxtacellular administration of GLP 1 ( 7 36 ) amide first increased and then decreased single unit activities recorded in the hippocampal CA 1 , which effects were antagonized by exendin ( 9 39 ) amide , a GLP 1 receptor antagonist , or 6 cyano 7 nitroquinoxaline 2 , 3 dione , a non NMDA type glutamate receptor antagonist . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
We have recently reported that isolated islets from mice homozygous for a GLP 1 receptor null mutation ( GLP 1R ( / ) ) exhibit a well preserved insulin secretory response to glucose . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
It is an important incretin hormone ; mice with a null mutation in the GLP 1 receptor gene develop glucose intolerance . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In the first experiment , ICV infusion of a GLP 1 receptor antagonist [ exendin 4 ( 3 39 ) ] significantly attenuated ( 10 microgram dose ) or completely blocked ( 20 microgram dose ) the inhibition of food intake produced by subsequent ICV infusion of GLP 1 ( 7 36 ) amide ( 5 microgram ) . ^^^ In the second experiment , rats were infused with 0 , 10 , or 20 microgram of the GLP 1 receptor antagonist ICV , followed by injection of 0 . 15 M LiCl ( 50 mg / kg ip ) or the same volume of 0 . 15 M NaCl . ^^^ The ability of LiCl treatment to suppress food intake was significantly attenuated in rats that were pretreated with the GLP 1 receptor antagonist . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Finally , the GLP 1 receptor antagonist exendin 3 ( 9 39 ) inhibited the actions of GLP 1 . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
It is well known that the GLP 1 receptor is highly specific for GLP 1 and does not bind other peptides of the glucagon superfamily . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Male GLP 1 receptor knockout ( GLP 1R / ) mice exhibit reduced gonadal weights , and females exhibit a slight delay in the onset of puberty ; however , male and female GLP 1R / animals reproduce successfully and respond appropriately to fluid restriction . ^^^ These findings suggest that although GLP 1R signaling is not essential for development and basal function of the murine hypothalamic pituitary adrenal axis , abrogation of GLP 1 signaling is associated with impairment of the behavioral and neuroendocrine responses to stress . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Furthermore , the GLP 1 receptor is expressed in both neurons and glia . ^^^ Because after a penetrating injury a large population of astrocytes become activated and augment their expression of numerous substances , we have used in situ hybridization to determine whether the expression of the GLP 1 receptor increases in response to a penetrating injury . ^^^ We have found that GLP 1 receptor expression increases dramatically along the border of the injury . ^^^ Furthermore , this expression can be colocalized to glial fibrillary acidic protein ( GFAP ) and non GFAP mRNA containing cells , suggesting that at least part of this increase is due to an increase in GLP 1 receptor expression in glial cells . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Thus , regionally distinct GLP 1 receptor populations in the CNS may be involved in satiety or malaise . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
To test this hypothesis , we pretreated rats with a selective and potent GLP 1 receptor antagonist given directly into the third ventricle via an indwelling cannula before administration of peripheral LiCl . ^^^ The GLP 1 receptor antagonist completely blocked the effect of LiCl to reduce food intake , induce pica , and produce a conditioned taste aversion . ^^^ The same dose of GLP 1 receptor antagonist did not reverse the LiCl induced reduction in NaCl intake . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
GLP 1 receptor affinity was highest for imi GLP 1 , followed by alpha me GLP 1 and N me GLP 1 . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The hepatic vagal reception of intraportal GLP 1 is via receptor different from the pancreatic GLP 1 receptor . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
GLP 1 had a potency ( EC ( 50 ) ) of 55 pM for the cloned human GLP 1 receptor . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
This inhibitor also improved glucose tolerance in GLP 1 receptor ( / ) mice , indicating that CD 26 contributes to blood glucose regulation by controlling the activity of GLP 1 as well as additional substrates . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Intracerebroventricular administration of the GLP 1 receptor antagonist exendin ( 9 39 ) ( 10 nmol / rat ) reversed the increases induced by GLP 1 ( 500 pmol / rat ; P < 0 . 01 ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In contrast to previous studies , these findings show that peripheral ( s . c . ) administration of both GLP 1 receptor agonists also induces satiety and weight loss in rats , and suggest the potential usefulness of exendin 4 as a therapeutic tool for the treatment of diabetes and / or obesity . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The GLP 1 receptor agonist exendin 4 showed similar effects , whereas the receptor antagonist exendin ( 9 39 ) amide inhibited the GLP 1 induced increase in insulin receptor binding . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
GLP 1 produced a dose dependent stimulation of 410RIP1 LUC ( EC 50 0 . 43 nmol / l ) , an effect reproduced by the GLP 1 receptor agonist exendin 4 and abolished by the antagonist exendin ( 9 39 ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
As GLP 1 exhibits a short t ( 12 ) in vivo , the biological consequences of prolonged GLP 1 receptor signaling remains unclear . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Exendin ( 9 39 ) amide , a GLP 1 receptor antagonist , prevented the GLP 1 induced depolarization . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
To determine the physiological importance of GLP 1 receptor ( GLP 1R ) leptin interactions , we studied islet function and feeding behavior in ob / ob : GLP 1R ( / ) mice . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In contrast , no constitutive activity was observed for GLP 1 receptor , yet responses to GLP 1 indicated that receptor expression had taken place . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The effects of the incretin hormone glucagon like peptide 1 ( 7 36 ) amide ( GLP 1 ) are mediated by the GLP 1 receptor ( GLP 1R ) . ^^^ A novel silencer element repressing expression of the GLP 1 receptor gene in fibroblasts and pancreatic A cells , but not in pancreatic B and D cells . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Increases in plasma glucagon like peptide 1 ( GLP 1 ) levels and islet GLP 1 receptor mRNA supported increased insulin secretion by HC islets . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The purified N terminal fragment ( hereafter referred to as NT ) of the GLP 1R produced in either insect ( Sf 9 ) or mammalian ( COS 7 ) cells was shown to bind GLP 1 . ^^^ The GLP 1R NT protein attached to beads bound GLP 1 , but with lower affinity ( inhibitory concentration ( IC ( 50 ) ) : 4 . 5 10 10 ( 7 ) M ) than wild type ( WT ) GLP 1R ( IC ( 50 ) : 5 . 2 10 10 ( 9 ) M ) . ^^^ The low affinity of GLP 1R NT suggested that other receptor domains may contribute to GLP 1 binding . ^^^ GIP ( 1 151 ) / GLP 1R , but not GIP ( 1 222 ) / GLP 1R , exhibited specific GLP 1 binding and GLP 1 induced cAMP production , suggesting that the region encompassing transmembrane ( TM ) domain 1 through to TM 3 was required for binding . ^^^ These studies indicate that the NT domain of the GLP 1R is able to bind GLP 1 , but charged residues concentrated at the distal TM2 / extracellular loop 1 ( EC 1 ) interface ( K 197 , D 198 , K 202 ) and in EC 1 ( D 215 and R 227 ) probably contribute to the binding determinants of the GLP 1R . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The present study examined whether central GLP 1 receptor signaling plays a functional role in LPS induced fever . ^^^ Adult male Sprague Dawley rats were injected i . p . with LPS ( 0 or 100 microg / kg ) , then were infused intracerebroventricularly with GLP 1 receptor antagonist ( 0 or 10 microg ) delivered 2 . 5 h after injection of LPS or vehicle . ^^^ The pyrogenic effect of LPS was amplified in rats that received central infusion of GLP 1 receptor antagonist , although the antagonist by itself did not alter body temperature . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
GLP 1 receptor signaling appears essential for beta cell signal transduction as exemplified by studies of GLP 1R / mice . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
This review highlights recent advances in our understanding of GLP 1 physiology and GLP 1 receptor signaling , and summarizes current pharmaceutical strategies directed at sustained activation of GLP 1 receptor dependent actions for glucoregulation in vivo . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In contrast , coinfusion of glucose and the GLP 1 receptor antagonist exendin ( 9 39 ) into the portal vein at a rate of 0 . 5 pmol / kg . min ( P Ex mice ) reduced glucose clearance to 36 . 1 + / 2 . 6 ml / kg . min and transiently increased glycemia to 9 . 2 + / 0 . 3 mmol / l at 60 min of infusion before it returned to the fasting level ( 5 . 6 + / 0 . 3 mmol / l ) at 3 h . ^^^ Finally , portal vein infusion of glucose in GLP 1 receptor ( / ) mice failed to increase the glucose clearance rate ( 26 . 7 + / 2 . 9 ml / kg . min ) . ^^^ Together , our data show that the GLP 1 receptor is part of the hepatoportal glucose sensor and that basal fasting levels of GLP 1 sufficiently activate the receptor to confer maximum glucose competence to the sensor . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
As with GLP 1 Gly ( 8 ) , the binding affinity of GLP 1 Aha ( 8 ) for the GLP 1 receptor in intact Chinese hamster ovary ( CHO ) cells expressing the human GLP 1 receptor ( CHO / GLP 1R cells ) was reduced ( IC ( 50 ) : GLP 1 , 3 . 7 + / 0 . 2 nM ; GLP 1 Gly ( 8 ) , 41 + / 9 nM ; GLP 1 Aha ( 8 ) , 22 + / 7 nM ) . ^^^ They had poor binding affinity for the GLP 1 receptor , and none of these compounds stimulated the production of intracellular cAMP in CHO / GLP 1R cells or insulin secretion in RIN 1046 38 cells . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
CICR was triggered by the GLP 1 receptor agonist exendin 4 , an effect mimicked by caffeine , Sp cAMPS or forskolin . ^^^ It is concluded that CICR in INS 1 cells results from GLP 1 receptor mediated sensitization of the intracellular Ca2+ release mechanism , a signal transduction pathway independent of PKA , but which requires cAMP GEF II . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
GLP 1 containing nerve fibres and the GLP 1 receptor are found predominantly in hypothalamic midline nuclei . ^^^ In contrast to the widely distributed GLP 1 receptor mRNA , GLP 2 receptor mRNA is exclusively expressed in the compact part of the DMH ( DMHc ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In INS 1 cells over expressing the beta cell GLP 1 receptor ( GLP 1 R ) , we have shown , by radioimmune assay and bioassay of conditioned medium , that an autocrine signaling mechanism of hormone action exists whereby self secreted GLP 1 acts as a competence factor in support of insulin gene transcription . ^^^ The GLP 1 R agonist exendin 4 stimulates RIP 1 Luc activity in a glucose dependent manner , an effect mediated by endogenous GLP 1 Rs , and is blocked by the serine / threonine protein kinase inhibitor Ro 31 8220 . ^^^ Over expression of GLP 1 R in transfected INS 1 cells reduces the threshold for exendin 4 agonist action , whereas basal RIP 1 Luc activity increases 2 . 5 fold in the absence of added agonist . ^^^ The increase of basal RIP 1 Luc activity is a consequence of autocrine stimulation by self secreted GLP 1 and is blocked by introduction of ( 1 ) an inactivating W39A mutation in the N terminus ligand binding domain of GLP 1 R or ( 2 ) mutations in the third cytoplasmic loop that prevent G protein coupling . ^^^ No evidence for constitutive ligand independent signaling properties of the GLP 1 R has been obtained . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
High concentrations of glucagon like peptide 1 ( 7 36 ) amide ( GLP 1 ) and its specific receptor ( GLP 1R ) have been found in the rat hypothalamus . ^^^ In this study the actions of GLP 1 and its related peptides , exendin 4 ( GLP 1R agonist ) , exendin ( 9 39 ) ( GLP 1R antagonist ) and GLP 1 ( 9 36 ) amide ( the major GLP 1 metabolite ) on levels of serotonin ( 5 HT ) , 5 hydroxyindolacetic acid ( 5 HIAA ) and amino acids ( Glu , Asp , Gln , Gly , Tyr , Trp , GABA ) in the hypothalamus were investigated . ^^^ GLP 1 ( 9 36 ) amide , a primary metabolite of GLP 1 , appears to act as an endogenous antagonist at the GLP 1R . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
At the end of treatment , basal plasma GLP 1 levels were increased , and pancreatic gene expression for GLP 1 receptor was significantly upregulated . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In vitro folding , functional characterization , and disulfide pattern of the extracellular domain of human GLP 1 receptor . ^^^ The N terminal , extracellular domain of the receptor for glucagon like peptide 1 ( GLP 1 receptor ) was expressed at a high level in E . coli and isolated as inclusion bodies . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The effect of LY 315902 and GLP 1 on fasting small bowel motility was dose dependent and treatment with exendin ( 9 39 ) amide , a GLP 1 receptor antagonist , together with LY 315902 and GLP 1 completely antagonised the inhibitory effect of LY 315902 and GLP 1 on fasting small bowel motility . ^^^ The effect of LY 315902 on motor control is mediated through the GLP 1 receptor and seems partly dependent on the L arginine / NO pathway . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Further evidence for a GLP 1 receptor in this tissue , different from that of the pancreas , is also illustrated , suggesting a role for an inositolphosphoglycan ( IPG ) as at least one of the possible second messengers of the GLP 1 action in human muscle . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
We report on the effects of GLP 1 and two of its long acting analogs , exendin 4 and exendin 4 WOT , on neuronal proliferation and differentiation , and on the metabolism of two neuronal proteins in the rat pheochromocytoma ( PC 12 ) cell line , which has been shown to express the GLP 1 receptor . ^^^ We observed that GLP 1 and exendin 4 induced neurite outgrowth in a manner similar to nerve growth factor ( NGF ) , which was reversed by coincubation with the selective GLP 1 receptor antagonist exendin ( 9 39 ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The specificity of both antagonists was demonstrated by their selective interaction with glucagon receptor signaling in rat hepatocytes and GLP 1 receptor signaling in Chinese hamster lung ( CHL ) fibroblasts . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Furthermore , the contrasting responses of exendin and GLP 1 in 3T3 adipocytes suggest that the peripheral insulin sensitizing effect of exendin 4 ( in contrast to the insulinotropic effect ) does not involve the GLP 1 receptor pathway . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
No inhibition of influx by the selective GLP 1 receptor antagonist exendin ( 9 39 ) , suggesting that the GLP 1 receptor is not involved in the rapid entry into brain . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
GLP 1 receptor signaling contributes to anorexigenic effect of centrally administered oxytocin in rats . ^^^ In the first experiment , rats were infused centrally with GLP 1 receptor antagonist or vehicle , followed by an anorexigenic dose of synthetic OT . ^^^ The anorexigenic effect of OT was eliminated in rats pretreated with the GLP 1 receptor antagonist . ^^^ These findings implicate endogenous GLP 1 receptor signaling as an important downstream mediator of anorexia in rats after activation of central OT neural pathways . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Although GLP 1 receptor ( GLP 1R ) agonists are under development for the treatment of diabetes , GLP 1 administration may increase blood pressure and heart rate in vivo . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
We have investigated the acute effects of preproglucagon derived peptides ( PGDP ) glucagon , glucagon like peptide 1 ( GLP 1 ) , glucagon like peptide 2 ( GLP 2 ) , and exendin 4 ( EX 4 ) , a GLP 1 receptor agonist , on thyrotropin ( TSH ) secretion in the rat . ^^^ Moreover , obtained results suggest that both EX 4 and EX ( 9 39 ) evoked inhibition of TSH secretion in the rat is not dependent on their interaction with GLP 1 receptor only . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The mechanism by which DMSO imparts this amplifying action is unclear but may involve redistribution of intracellular compartments or a direct molecular interaction with a downstream target of the GLP 1 receptor signaling pathway in the beta cell . ^^^ These effects of DMSO on incretin action may provide novel applications with respect to further characterizing GLP 1 receptor signaling , identifying incretin like compounds in screening assays , and as a therapeutic treatment in type 2 diabetes . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Exendin 4 ( 1 39 ) ( Ex 4 ) , isolated from Gila monster venom , is a highly specific GLP 1 receptor agonist that exhibits a prolonged duration of action in vivo . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
GLP 1 reduced recombinant K ( ATP ) channel currents by 54 . 1 + / 6 . 9 % in mammalian cells coexpressing SUR 1 , Kir6 . 2 , and GLP 1 receptor clones . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The glucagon like peptide 1 receptor binding site for the N terminus of GLP 1 requires polarity at Asp 198 rather than negative charge . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
We examined whether GLP 1 receptor signaling modifies the cellular susceptibility to apoptosis . ^^^ Conversely , mice with a targeted disruption of the GLP 1 receptor gene exhibited increased beta cell apoptosis after STZ administration . ^^^ These findings demonstrate that GLP 1 receptor signaling directly modifies the susceptibility to apoptotic injury , and provides a new potential mechanism linking GLP 1 receptor activation to preservation or enhancement of beta cell mass in vivo . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Additionally , expression of the GLP 1 receptor in whole pancreas was increased 2 . 3 fold in the fat fed dogs . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In addition , bilateral CeA administration of 2 . 5 microg of a GLP 1 receptor antagonist before intraperitoneal administration of the toxin lithium chloride resulted in a diminished CTA . ^^^ Together , these data indicate that separate GLP 1 receptor populations mediate the multiple responses to GLP 1 . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Exendin 4 is an agonist of the GLP 1 receptor . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Here , we report that GLP 1 receptor signaling also regulates the activity of beta cell voltage dependent K ( + ) ( K ( 5 ) ) channels , themselves potent glucose dependent regulators of insulin secretion . ^^^ GLP 1 receptor activation with exendin 4 ( 10 ( 8 ) mol / l ) in rat beta cells antagonized K ( 5 ) currents by 43 . 3 + / 6 . 3 % , whereas the GLP 1 receptor antagonist exendin 9 39 had no effect . ^^^ The effect of GLP 1 receptor activation on K ( 5 ) currents could be replicated ( current reduction of 55 . 7 + / 6 . 0 % ) by G protein activation with GMP PNP ( 10 nmol / l ) . ^^^ The cAMP pathway antagonist Rp cAMPS ( 100 micro mol / l ) prevented current inhibition by exendin 4 , implicating cAMP signaling in GLP 1 receptor modulation of beta cell K ( 5 ) currents . ^^^ The present results demonstrate that GLP 1 receptor signaling can antagonize beta cell repolarization by reducing voltage dependent K ( + ) currents , an effect likely to contribute to GLP 1 ' s glucose dependent insulinotropic effect . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
However , the exact mechanism by which the GLP 1 receptor ( GLP 1R ) , a member of the G protein coupled receptor ( GPCR ) superfamily , activates the PI 3 kinase signaling pathway to promote beta cell growth remains unknown . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
We have recently reported that GLP 1 and several longer acting analogs that bind at the GLP 1 receptor , possess neurotrophic properties , and offer protection against glutamate induced apoptosis and oxidative injury in cultured neuronal cells . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Competition binding studies demonstrated that the N terminal domain of the GLP 1 receptor maintains high affinity for the agonist exendin 4 as well as the antagonists exendin 4 ( 3 39 ) and exendin 4 ( 9 39 ) whereas , in contrast , GLP 1 affinity was greatly reduced . ^^^ These data are consistent with a model for the binding of peptide ligands to the GLP 1 receptor in which the central and C terminal regions of the peptides bind to the N terminus of the receptor , whereas the N terminal residues of peptide agonists interact with the extracellular loops and transmembrane helices . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Both GLP 1 receptor and GIP receptor knockout mice ( GLP 1R ( / ) and GIPR ( / ) , respectively ) have been generated to investigate the physiological importance of this axis . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
We examined beta cell mass regeneration after 70 % Ppx in mice receiving the GLP 1 antagonist Ex 9 39 and in GLP 1R ( / ) mice . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The CJC 1131 albumin conjugate bound to the GLP 1 receptor ( GLP 1R ) and activated cAMP formation in heterologous fibroblasts expressing a GLP 1R . ^^^ These findings demonstrate that an albumin conjugated DAC : GLP 1 mimics the action of native GLP 1 and represents a new approach for prolonged activation of GLP 1R signaling . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
These findings demonstrate the benefits of a 3 h infusion of GLP 1 on beta cell function beyond those of an acute insulin secretagogue , and support the development of strategies using continuous or prolonged GLP 1 receptor agonism for treating diabetic patients . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
AIMS / HYPOTHESIS : This study examined the biological effects of the GIP receptor antagonist , ( Pro 3 ) GIP and the GLP 1 receptor antagonist , exendin ( 9 39 ) amide . ^^^ In GLP 1 receptor transfected fibroblasts , exendin ( 9 39 ) amide inhibited GLP 1 stimulated cyclic AMP production with maximal inhibition of 60+ / 0 . 7 % at 10 ( 6 ) mol / l , whereas ( Pro ( 3 ) ) GIP had no effect . ( Pro ( 3 ) ) GIP specifically inhibited GIP stimulated insulin release ( 86 % ; p < 0 . 001 ) from clonal BRIN BD 11 cells , but had no effect on GLP 1 stimulated insulin release . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
We have shown that activation of the GLP 1 receptor inhibits H ( 2 ) O ( 2 ) induced apoptosis in a cultured mouse insulinoma cell line , termed MIN 6 . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The natural GLP 1 receptor agonist exendin 4 , found in the saliva of the Gila monster , has a longer biological half life after subcutaneous injection than GLP 1 , and inhibition of DPP 4 using , for example , pyrrolidine derivatives provides elevated concentrations of intact , biologically active GIP and GLP 1 endogenously released from the gut . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
GLP 1 receptor agonists are growth and differentiation factors for pancreatic islet beta cells . ^^^ This leads us to propose that GLP 1 and GLP 1 receptor agonists , in the context of long term treatment of type 2 diabetes , will have broader biological action on the endocrine pancreas than was earlier anticipated . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
It is secreted primarily in two forms , GLP 1 ( 7 37 ) and GLP 1 ( 7 36 ) NH ( 2 ) , both of which bind to a specific GLP 1 receptor ( GLP 1r ) on the pancreatic beta cell and augment glucose stimulated insulin secretion . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Both intravenous and intracerebroventricular administration of GLP 1 receptor ( GLP 1R ) agonists increase blood pressure and heart rate and induce Fos like immunoreactivity ( Fos IR ) in autonomic regulatory sites in the rat brain . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The GLP 1 / 2 containing neural pathways have been suggested to play a role in taste aversion and nausea because LiCl activates these neurons , and LiCl induced suppression of food intake can be blocked by the GLP 1 receptor antagonist exendin 9 . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Substitution of distinct segments of the glucagon receptor core domain with the corresponding segments of the GLP 1 receptor rescued the affinity and potency of specific glucagon analogs . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Glucagon like peptide 1 ( GLP 1 ) acts via its G protein coupled receptor ( GLP 1R ) to regulate blood glucose . ^^^ Although the GLP 1R is widely expressed in peripheral tissues , including the heart , and exogenous GLP 1 administration increases heart rate and blood pressure in rodents , the physiological importance of GLP 1R action in the cardiovascular system remains unclear . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
It was recently reported that GLP 1 and exendin 4 , a naturally occurring , more stable analogue of GLP 1 that binds at the GLP 1 receptor , possess neurotrophic properties and can protect neurons against glutamate induced apoptosis . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Finally , we examined the local role of endogenous GLP 1 by specific GLP 1 receptor blockade . ^^^ LH microinjections of exendin ( 9 39 ) amide , a GLP 1 receptor antagonist , at 1 or 2 . 5 microg did not alter feeding behavior in 24 h fasted rats . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The delay in crop emptying induced by GLP 1 ( 15 pmol ) was partly attenuated by co administration with exendin ( 5 39 ) ( 600 pmol ) , a GLP 1 receptor antagonist , although exendin ( 5 39 ) alone did not affect crop emptying . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
We found that removing these AAs from Ex 4 to produce Ex ( 1 30 ) reduced the affinity for the GLP 1 receptor ( GLP 1R ) relative to Ex 4 ( IC 50 : Ex 4 , 3 . 22+ / 0 . 9 nM ; Ex ( 1 30 ) , 32+ / 5 . 8 nM ) but made it comparable to that of GLP 1 ( IC 50 : 44 . 9+ / 3 . 2 nM ) . ^^^ The importance of the nine amino acid C terminal sequence of exendin 4 for binding to the GLP 1 receptor and for biological activity . ^^^ The addition of this nine AA sequence to GLP 1 improved the affinity of both GLP 1 and the DPP 4 resistant analog GLP 1 8 glycine for the GLP 1 receptor ( IC 50 : GLP 1 Gly 8 [ GG ] , 220+ / 23 nM ; GLP 1 Gly 8 Ex ( 31 39 ) , 74+ / 11 nM ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Exendin 4 , a GLP 1 receptor agonist , interacts with proteins and their products of digestion to suppress food intake in rats . ^^^ The GLP 1 receptor agonist , Exendin 4 ( Ex 4 ) ( 0 . 5 micro g / rat ) , was given intraperitoneally to male Wistar rats , and food intake was measured when Ex 4 was given alone or with preloads of intact whey and casein proteins , their hydrolysates and amino acid mixtures ( 0 . 5 g 10 4 mL ( 1 ) 10 rat ( 1 ) ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The GLP 1 receptor ( GLP 1R ) antagonist Ex ( 9 39 ) did not significantly affect ACTH , aldosterone and cortico sterone responses to Ex 4 . ^^^ Exendin 4 , a GLP 1 receptor agonist , stimulates pituitary adrenocortical axis in the rat : Investigations into the mechanism ( s ) underlying Ex 4 effect . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
This is due , at least in part , to a heightened response of the mutant GLP 1 receptor to multiple sources of the somatic ligand LAG 2 , including the proximal somatic gonad . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
To develop non beta cells that exhibit physiologically regulated insulin secretion , we coexpressed the GLP 1 receptor and human insulin in primary rat pituitary cells using adenovirus mediated gene transfer . ^^^ Normal pituitary cells do not express the GLP 1 receptor as shown by the absence of GLP 1 receptor mRNA and the inability of GLP 1 to stimulate pituitary hormone secretion . ^^^ Following transduction with an adenovirus carrying the GLP 1 receptor cDNA , the pituitary cells expressed functional GLP 1 receptors as reflected by the ability of GLP 1 to stimulate secretion of pituitary hormones . ^^^ When both the GLP 1 receptor and human insulin were introduced , GLP 1 stimulated cosecretion of human insulin and endogenous pituitary hormones . ^^^ After transplantation of pituitary cells coexpressing human insulin and GLP 1 receptor into mice , enteral glucose stimulated insulin secretion . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Glucagon like peptide 1 ( GLP 1 ) is a gut peptide that , together with its receptor , GLP 1R , is expressed in the brain . ^^^ Here we show that intracerebroventricular ( i . c . v . ) GLP 1 and [ Ser ( 2 ) ] exendin ( 1 9 ) ( HSEGTFTSD ; homologous to a conserved domain in the glucagon / GLP 1 family ) enhance associative and spatial learning through GLP 1R . [ Ser ( 2 ) ] exendin ( 1 9 ) , but not GLP 1 , is also active when administered peripherally . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Coexpression of the CaSR and GLP 1 receptor ( GLP 1R ) produces a pertussis toxin sensitive inhibition of GLP 1 induced cAMP production in response to elevated extracellular [ Ca2+ ] . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Successful strategies to overcome this difficulty are the use of DPPIV resistant GLP 1 receptor agonists , such as NN 2211 or exendin 4 , and the use of inhibitors of DPPIV , such as NVPDPP 728 and P32 / 98 . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Receptor binding studies demonstrated that the affinity of ZP10A for the human GLP 1 receptor was 4 fold greater than the affinity of GLP 1 ( 7 36 ) amide . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
CONCLUSION / INTERPRETATION : This study identifies type 8 AC in insulin secreting cells as one of the potential molecular targets for synergism between GLP 1 receptor mediated and glucose mediated signalling . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
However , native GLP 1 is rapidly degraded by DPP 4 after parenteral administration ; hence , degradation resistant , long acting GLP 1 receptor ( GLP 1R ) agonists are preferable agents for the chronic treatment of human diabetes . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
AC 2993 ( Exendin 4 ) is a naturally occurring peptide isolated from the lizard Heloderma , and it acts as a high affinity agonist at the GLP 1 receptor . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In the adult hermaphrodite , reduction of SEC 23 function by RNA mediated interference caused a rapid onset of sterility , with defects in oogenesis including early maturation of the germline nuclei , probably a result of the observed loss of the GLP 1 receptor from the membrane surfaces adjacent to the developing germline nuclei . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The mechanism and signaling pathway regulating these currents in rat beta cells were investigated using the GLP 1 receptor agonist exendin 4 . ^^^ Therefore , antagonism of beta cell Kv currents by GLP 1 receptor activation requires both cAMP / PKA and PI 3 kinase / PKCzeta signaling via trans activation of the EGF receptor . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Glucagon like peptide ( GLP ) 1 binds to GLP 1 receptor ( with a Kd of 0 . 2 nM ) signals through Galpha ( s ) to activate adenylate cyclase , which results in an increase of intracellular cAMP ( EC ( 50 ) of 0 . 3 nM ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Despite evidence that the GLP 1 receptor is present and active in neurons , little is known of the roles of GLP 1 in neuronal physiology . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Glucagon like peptide 1 ( GLP 1 ) and GLP 1 receptor agonists increase the beta cell mass in rodent models of type 2 diabetes and enhance the proliferation rate of beta cells in vitro , while the long term effect in vivo in non diabetic animals is unknown . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Gene expression of the GLP 1 receptor was clearly detected by both RT PCR and Northern blot analysis . ^^^ However , semi quantitative RT PCR revealed that the ratio of the gene expression level of the GIP receptor to that of the GLP 1 receptor was less than 1 : 250 , indicating that receptor gene expression of GIP is practically negligible in the ganglion . ^^^ Additionally , an equal level of GLP 1 receptor gene expressions between left and right side ganglia was evidenced by semi quantitative RT PCR , implying possible extrahepatic occurrence of vagal GLP 1 reception in addition to the reception through the hepatic vagus ( originating from the left side ganglion ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
This analogue , ( Lys ( 9 ) ) GLP 1 , exhibited a preserved GLP 1 receptor affinity , but the usual stimulatory effects of GLP 1 were completely eliminated , a trait duplicated by the other established GLP 1 antagonists , exendin ( 9 39 ) and GLP 1 ( 9 36 ) amide . ^^^ We investigated the in vivo antagonistic actions of ( Lys ( 9 ) ) GLP 1 in comparison with GLP 1 ( 9 36 ) amide and exendin ( 9 39 ) and revealed that this novel analogue may serve as a functional antagonist of the GLP 1 receptor . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The primary ligand binding interaction at the GLP 1 receptor is via the putative helix of the peptide agonists . ^^^ The N terminal domain of the GLP 1 receptor binds the putative helical region of the peptide agonists , GLP 1 and exendin 4 . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Met 204 and Tyr 205 are together important for binding GLP 1 receptor agonists but not their N terminally truncated analogues . ^^^ A mutagenesis study to systematically analyse residues spanning the first extracellular loop of the GLP 1 receptor identified a double mutant , Met 204 / Tyr 205 Ala / Ala , which displayed : markedly reduced affinity for the natural agonist GLP 1 ; slightly reduced affinity for its analogue exendin 4 ; and unaltered affinity for several N terminally truncated analogues of GLP 1 and exendin 4 . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
RESULTS : OXM activates signaling pathways in cells through glucagon or GLP 1 receptors ( GLP 1R ) but transiently inhibits food intake in vivo exclusively through the GLP 1R . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
We report that Albugon , a human glucagon like peptide ( GLP ) 1 albumin recombinant protein , activates GLP 1 receptor ( GLP 1R ) dependent cAMP formation in BHK GLP 1R cells , albeit with a reduced half maximal concentration ( EC ( 50 ) ) ( 0 . 2 vs . 20 nmol / l ) relative to the GLP 1R agonist exendin 4 . ^^^ A recombinant human glucagon like peptide ( GLP ) 1 albumin protein ( albugon ) mimics peptidergic activation of GLP 1 receptor dependent pathways coupled with satiety , gastrointestinal motility , and glucose homeostasis . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The GLP 1 HSA bioconjugates were analyzed in vitro to assess the stabilizing effect of bioconjugation in the presence of DPP 4 as well as GLP 1 receptor binding and activation . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
To address the possibility that the partial disruption of Glucagon like peptide 1 ( GLP 1 ) signaling could cause diabetes , we tried to detect the mutation in GLP 1 receptor ( GLP 1R ) gene in the population with type 2 diabetes . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
GLP 1 receptor agonists depolarized hypocretin neurons and increased their spike frequency ; the antagonist exendin ( 9 39 ) blocked this depolarization . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Most compellingly , pharmacological antagonists of the GLP 1 receptor ( GLP 1R ) block several effects of LiCl in rat . ^^^ The major goal of these experiments was to further test the hypothesis that the central nervous system GLP 1 system is critical to the visceral illness actions of LiCl by using mice with a targeted disruption of the only described GLP 1R . ^^^ Although lateral ventricular GLP 1 produced a CTA in wild type mice , it did not produce a CTA in GLP 1R / mice . ^^^ To test the possibility that alternate GLP 1Rs mediate aversive effects , we examined the ability of GLP 1 to produce a CTA in GLP1R / mice . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The actions of glucagon were unaffected by the GLP 1 receptor antagonist exendin ( 9 39 ) but abolished by des His 1 [ Glu 9 ] glucagon amide , a specific blocker of the glucagon receptor . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Attenuation of lipopolysaccharide anorexia by antagonism of caudal brain stem but not forebrain GLP 1 R . ^^^ Here we explore GLP 1 mediation of the anorexic response to administration of systemic LPS and address the relative importance of caudal brain stem and forebrain GLP 1 receptor ( GLP 1 R ) for the mediation of the response . ^^^ Fourth intracerebroventricular delivery of the GLP 1 R antagonist exendin ( 9 39 ) ( 10 microg ) did not itself affect food intake in the 24 h after injection but significantly attenuated the otherwise robust ( approximately 60 % ) reduction in food intake obtained after LPS ( 100 microg / kg ) treatment . ^^^ This result highlights a role for caudal brain stem GLP 1 R in the mediation of LPS anorexia but does not rule out the possibility that forebrain receptors also contribute to the response . ^^^ Forebrain contribution was addressed by delivery of the GLP 1 R antagonist to the third ventricle with the caudal flow of cerebrospinal fluid blocked by occlusion of the cerebral aqueduct . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
To prolong GLP 1 bioactivity , DPPIV resistant GLP 1 analogues , DPPIV inhibitors and exenatide , a long acting synthetic GLP 1 receptor agonist derived from the Gila monster hormone exendin 4 , have been developed . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
These effects are thought to be mediated by the GLP 1 receptor . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Chronic exposure to GLP 1R agonists promotes homologous GLP 1 receptor desensitization in vitro but does not attenuate GLP 1R dependent glucose homeostasis in vivo . ^^^ The rapid degradation of native GLP 1 has engendered interest in more stable longer acting GLP 1 receptor agonists such as exendin 4 ( Ex 4 ) ; however , the potential consequences of sustained GLP 1 receptor activation leading to receptor desensitization has not been extensively studied . ^^^ We have now examined a range of GLP 1 receptor dependent responses following treatment with Ex 4 using INS 1 cells in vitro and both wild type control and MT Ex 4 transgenic mice in vivo . ^^^ Although both GLP 1 and Ex 4 acutely desensitized GLP 1 receptor dependent cAMP accumulation in INS 1 cells , Ex 4 produced more sustained receptor desensitization , relative to GLP 1 , in both acute ( 5 120 min ) and chronic ( 24 72 h ) experiments . ^^^ Similarly , the levels of insulin , pdx 1 , and GLP 1 receptor mRNA transcripts were comparable in wild type and MT Ex 4 transgenic mice after 1 week of Ex 4 administration . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Furthermore , the GLP 1 receptor agonist , Exenatide , dose dependently enhanced phosphorylation of S6K1 at an intermediate glucose concentration ( 8 mmol / l ) in a rapamycin sensitive manner . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The relaxant effect from GLP 1 was completely inhibited by the specific GLP 1 receptor antagonist , exendin ( 9 39 ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The augmented insulin response to GRP by val pyr was prevented by the GLP 1 receptor antagonist , exendin ( 3 ) ( 9 39 ) , raising the possibility that GRP effects may occur secondary to stimulation of GLP 1 secretion . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
This protection was abolished in the in vitro hearts by the GLP 1 receptor antagonist exendin ( 9 39 ) , the cAMP inhibitor Rp cAMP , the PI3kinase inhibitor LY 294002 , and the p42 / 44 mitogen activated protein kinase inhibitor UO 126 . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Activity of secreted GLP 1 Gly 8 was assayed using Chinese hamster lung fibroblasts ( CHL ) cells that expressed cloned GLP 1 receptor and that were transfected with CRE Luc . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Analysis of mice with inactivation of the GLP 1 receptor gene has provided evidence that absence of GLP 1 action in the mouse , despite this hormone potent physiological effects when administered in vivo , only leads to mild abnormalities in glucose homeostasis without any change in body weight . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The GLP 1 receptor is a Class B heptahelical G protein coupled receptor that stimulates cAMP production in pancreatic beta cells . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
From these results we conclude that while GLP 1 does not seem to induce beta cell lipolysis acutely in mouse islets , the peptide affects beta cell fat metabolism after long term adaptation to GLP 1 receptor stimulation . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Thus , GLP 1 receptor agonists are being intensively developed for the treatment of human diabetes and are likely to become available to clinical use in the near future . ^^^ Evidence suggesting a role for endogenous GLP 1 and GLP 1 receptor during beta cell development will be reviewed . ^^^ Finally , the therapeutic potential for intervention with GLP 1 receptor agonists during the neonatal period will be discussed . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
For more long term metabolic control , incretin mimetics ( agonists at the GLP 1 receptor ) with more favourable pharmacokinetic profiles should be used . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
GLP 1 receptor agonists and DPP 4 inhibitors in the treatment of type 2 diabetes . ^^^ One is to use GLP 1 receptor agonists that have a prolonged half life due to reduced degradation by DPP 4 . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
We determined the role of the islet beta cell and the pancreatic duodenal homeobox 1 ( Pdx 1 ) transcription factor for GLP 1 receptor ( GLP 1R ) dependent actions through analysis of mice with beta cell specific inactivation of the Pdx 1 gene ( beta cell ( Pdx 1 / ) mice ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
A GLP 1R antagonist significantly reduced insulin secretion / production in beta TC 6 insulinoma cells and isolated rat islets , suggesting a functionally important loop between locally produced GLP 1 and its cognate receptor . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
New therapeutic strategies and drug candidates for neurodegenerative diseases : p 53 and TNF alpha inhibitors , and GLP 1 receptor agonists . ^^^ Such targets include TNF alpha , p 53 , and GLP 1 receptor . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Specific binding of 125I GLP 1 ( 7 36 ) amide to the GLP 1R was detected in several brain areas and was inhibited by unlabelled GLP 1 ( 7 36 ) amide , exendin 4 and exendin ( 9 39 ) . ^^^ The expression of GLP 1 receptor mRNA and protein allows the effect of GLP 1 on glucose metabolism in the human hypothalamus and brainstem . ^^^ In situ hybridization histochemistry revealed specific labelling for GLP 1 receptor mRNA in several brain areas . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In addition , induction of Pdx 1 suppressed the expression of glucagon like peptide 1 receptor ( GLP 1R ) , which resulted in marked reduction of both basal and GLP 1 agonist exendin 4 stimulated cellular cAMP levels . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Human studies employing the specific GLP 1 receptor antagonist exendin ( 9 39 ) show that endogenously released GLP 1 likewise controls fasting plasma glucagon , stimulates insulin , and influences all the motoric mechanisms known to control gastric emptying . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
One strategy is the use of DPP 4 resistant GLP 1 receptor agonists ( exenatide and liraglutide ) and another strategy is to inhibit DPP 4 activity ( LAF 237 ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Exendin ( 9 39 ) , described as a GLP 1 receptor antagonist , inhibited contraction due to glicentin or GLP 1 . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The endogenous beta cell GLP 1 receptor is coupled to adenylyl cyclase , cell depolarization , activation of voltage dependent Ca2+ channels ( VDCC ) and extracellular Ca2+ influx ( Lu et al . , 1993 b ) . ^^^ In contrast , the signaling pathways of the GLP 1 receptor in alpha cells are poorly understood . ^^^ To determine the signaling mechanisms of the alpha cell GLP 1 receptor , we established a stable pancreatic islet alpha cell line expressing the recombinant rat GLP 1 receptor ( INR 1 SF2 ) , using INRl G 9 cells . ^^^ These INRl G 9 cells do not express endogenous GLP 1 receptor . ^^^ This study establishes that a single GLP 1 receptor species can mediate the effects of GLP 1 through multiple signaling pathways , including the adenylyl cyclase system and intracellular Ca2+ release , in an alpha cell type . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The anti apoptotic effect of liraglutide was mediated by the GLP 1 receptor as the specific GLP 1 receptor antagonist , exendin ( 9 39 ) , blocked the effects . ^^^ In conclusion , GLP 1 receptor activation has anti apoptotic effect on both cytokine , and free fatty acid induced apoptosis in primary islet cells , thus suggesting that the long acting GLP 1 analogue , liraglutide , may be useful for retaining beta cell mass in both type 1 and type 2 diabetic patients . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In this work we analysed the substitution of Cys 438 by alanine in the glucagon like peptide 1 ( GLP 1 ) receptor ( GLPR ) , which led to a threefold decrease in cAMP production , although endocytosis and cellular redistribution of GLP 1 receptor agonist induced processes were unaffected . ^^^ Thus , cysteine 438 in the cytoplasmic tail of the GLP 1 receptor would regulate its interaction with G proteins and the stimulation of adenylyl cyclase . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
This study has employed the GLP 1 receptor antagonist , exendin 4 ( 9 39 ) amide ( Ex ( 9 39 ) ) to evaluate the role of endogenous GLP 1 in genetic obesity related diabetes and related metabolic abnormalities using ob / ob and normal mice . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In rat insulin secreting INS 1 cells or mouse beta cells loaded with caged Ca2+ ( NP EGTA ) , a GLP 1 receptor agonist ( exendin 4 ) is demonstrated to sensitize intracellular Ca2+ release channels to stimulatory effects of cytosolic Ca2+ , thereby allowing CICR to be generated by the uncaging of Ca2+ ( UV flash photolysis ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Expression and purification of exendin 4 , a GLP 1 receptor agonist , in Escherichia coli . ^^^ Exendin 4 is a potent and long acting agonist of GLP 1 receptor . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Hyperglycemia after protein ingestion concurrent with injection of a GLP 1 receptor agonist in rats : a possible role for dietary peptides . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Pretreatment with exendin ( 9 39 ) , a GLP 1 receptor antagonist , attenuated the leptin induced increase in CRH content of the hypothalamus . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Pre treatment with exendin 4 ( 10 ( 7 ) mol / l ) , a long acting GLP 1 receptor agonist , partially protected the cells against cytokine induced toxicity ( p < 0 . 01 ) in association with a reduction in cytokine induced inhibition of PKB phosphorylation ( p < 0 . 05 ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Male C57BL / 6 mice were injected ( ip ) with exendin 4 ( 1 39 ) ( Ex 4 , a GLP 1 receptor agonist ) and / or PYY ( 3 36NH2 ) ( 0 . 03 3 microg ) , and FI was determined for up to 24 h . ^^^ Similarly , exendin 4 ( 9 39 ) ( a GLP 1 receptor antagonist ) partially abolished Ex 4 induced anorexia ( P < 0 . 05 ) , but did not affect the satiation produced by PYY ( 3 36NH2 ) . ^^^ Thus , Ex 4 and PYY ( 3 36NH2 ) suppress FI via independent mechanisms involving a GLP 1 receptor dependent , sensory afferent pathway ( Ex 4 ) and a Y 2 receptor mediated pathway ( PYY ( 3 36NH2 ) ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Finally , we provided results to suggest that the transdifferentiated cells are functional by detecting : ( 1 ) functional markers for pancreatic beta cells including prohormone convertase 1 / 3 ( PC1 / 3 ) , insulin C peptide and glucagon like peptide 1 receptor ( GLP 1R ) , ( 2 ) increased insulin mRNA expression after treatment of cells with GLP 1 and betacellulin , physiological stimuli that regulate pancreatic function and ( 3 ) elevated insulin secretion after glucose challenge . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
We previously reported that GLP 1 and exendin 4 , a naturally occurring , long acting analogue of GLP 1 that binds the GLP 1 receptor ( GLP 1R ) , possess neurotrophic properties . ^^^ Enhancing central nervous system endogenous GLP 1 receptor pathways for intervention in Alzheimer ' s disease . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
A GLP 1 receptor ( GLP 1R ) polymorphism in which threonine 149 is substituted with a methionine residue has been recently identified in a patient with type 2 diabetes but was not found in non diabetic control subjects . ^^^ Compared to the wild type receptor , the variant GLP 1R showed ( 1 ) similar expression levels , ( 2 ) 60 and 5 fold reduced binding affinities , respectively , for two GLP 1R full agonists , GLP 1 and exendin 4 , and ( 3 ) markedly decreased potencies of these peptides in triggering cAMP mediated signaling ( despite conserved efficacies ) . ^^^ In contrast to full agonists , the efficacy of the primary GLP 1 metabolite / GLP 1R partial agonist , GLP 1 ( 9 36 ) amide , was essentially abolished by the T149M substitution . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Our findings indicate that the neighbouring trans membrane domain of the carboxyl terminal tail of the GLP 1 receptor contains sequence elements that regulate agonist dependent internalisation and transmembrane signalling . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
However , prolonged GLP 1 treatment resulted in GLP 1 receptor desensitization regardless of DPP 4 status . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
We showed previously that the C terminally truncated exendin peptide exendin ( 1 30 ) has a reduced affinity for the GLP 1 receptor and a diminished ability to increase intracellular cAMP in insulinoma cells . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The GLP 1 receptor was present at all five stages of the culture . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Acetaminophen concentrations , an indirect measurement of gastric emptying rate , were inversely correlated with total ghrelin concentrations ( saline r = 0 . 76 ; 95 % CI = 0 . 90 , 0 . 49 , GLP 1 r = 0 . 47 ; 95 % CI = 0 . 76 , 0 . 04 ) . ^^^ Ghrelin concentrations were only weakly correlated with insulin concentrations ( saline r = 0 . 36 ; 95 % CI = 0 . 69 , 0 . 09 ; GLP 1 r = 0 . 42 ; 95 % CI = 0 . 73 , 0 . 03 ) , but strongly inversely correlated with GIP concentrations ( saline r = 0 . 74 ; 95 % CI= 0 . 89 , 0 . 45 ; GLP 1 r = 0 . 63 ; 95 % CI = 0 . 84 , 0 . 27 ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The GLP 1 receptor is expressed in a variety of other tissues important for carbohydrate metabolism , including pancreatic alpha cells , hypothalamus and brainstem , and proximal intestinal tract . ^^^ Thus , because of its multiple actions , GLP 1 is an attractive therapeutic target for the treatment of type 2 diabetes , and major interest has resulted in the development of a variety of GLP 1 receptor agonists for this purpose . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
These results are consistent with exendin 4 having cardiovascular effects through GLP 1 receptor dependent and independent mechanisms , some of which involve sympathoadrenal activation . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The reduction of post prandial circulating active GLP 1 in Type 2 diabetic subjects , as a consequence of chronic hyperglycemia , could contribute to the reduction of early post prandial insulin secretion ; in fact , the administration of GLP 1 receptor antagonists to healthy volunteers elicits both an impairment of meal induced insulin secretion and an increase of post prandial glycemia similar to that observed in Type 2 diabetes . ^^^ There are now several compounds in various stages of pre clinical or clinical development for the treatment of Type 2 diabetes that utilize the GLP 1 signaling pathway ; these include GLP 1 receptor agonists with extended half lives , and inhibitors of DPP 4 that increase circulating levels of endogenous , intact and bioactive GLP 1 . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
In mice undergoing a hyperglycemic hyperinsulinemic clamp , icv administration of the specific GLP 1 receptor antagonist exendin 9 39 ( Ex 9 ) increased muscle glucose utilization and glycogen content . ^^^ Conversely , icv infusion of the GLP 1 receptor agonist exendin 4 ( Ex 4 ) reduced insulin stimulated muscle glucose utilization . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
AIMS : To assess the effects of endogenous GLP 1 on endocrine pancreatic secretion and antro pyloro duodenal motility by utilising the GLP 1 receptor antagonist exendin ( 9 39 ) amide ( ex ( 9 39 ) NH 2 ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The insulinotrophic effects of glucagon like peptide 1 ( GLP 1 ) are mediated by its seven transmembrane receptor ( GLP 1R ) in pancreatic beta cells . ^^^ Rapid ( 5 min ) stimulation of cAMP production was observed with 100 nM GLP 1 , 24 h after transfection of 2 microg GLP 1R DNA . ^^^ AtT 20 cells co transfected with GLP 1R and human glycoprotein hormone alpha subunit or rat POMC promoters revealed GLP 1 stimulated cAMP activation of transcription . ^^^ Co transfection of the pIRES vector with the GLP 1R resulted in GLP 1 stimulated activation of POMC promoter driven preproinsulin gene transcription but insulin secretion was not detected . ^^^ However , using an adenoviral expression system to infect AtT 20 cells with GLP 1R and the preproinsulin gene ( including 120 bp of its own promoter ) resulted in a 6 . 4 + / 0 . 6 fold increase in cAMP and a 4 . 9 + / 0 . 8 fold increase in insulin secretion in response to 100 nM GLP 1 . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The GLP 1 receptor agonist , exendin 4 , has a longer duration of action , and has recently been approved as a new agent for the treatment of type 2 diabetes mellitus . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
We mapped the positions of actively dividing germline nuclei in over 600 fixed gonad preparations including the wild type and a gain of function ligand responsive GLP 1 receptor mutant with an extended mitotic zone . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Administration of a GLP 1 receptor antagonist , GLP 1 ( 9 39 ) , resulted in decreased recovery of beta cells after STZ and worse glucose tolerance . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Targeted mutations were incorporated into the optimal dual receptor binding peptide to identify a peptide with the highly novel property of functioning as both a GLP 1 receptor agonist and a glucagon receptor antagonist . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
This article summarizes current concepts of incretin action and highlights the potential therapeutic utility of GLP 1 receptor agonists and dipeptidyl peptidase 4 ( DPP 4 ) inhibitors for the treatment of type 2 diabetes . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
GLP 1 acts via a G protein coupled receptor , and PI 3 Kgamma is known to be activated by G ( betagamma . ) Therefore , the role of PI 3 Kgamma in the chronic effects of GLP 1 on the beta cell was investigated using PI 3 Kgamma knockout ( KO ) mice treated with the GLP 1 receptor agonist , exendin 4 ( Ex 4 ; 1 nmol / kg sc every 24 h for 14 d ) . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
The GLP 1 receptor is widely distributed and has been identified in the endocrine pancreas , intestinal tract , brain , lung , kidney , and heart . ^^^ Here we report the expression of the GLP 1 receptor and proglucagon in the skin of newborn mice located predominantly in the hair follicles , as well as in cultures of skin derived cells that also express nestin , a marker of cultured cells that have dedifferentiated by epithelial to mesenchymal transition . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Glucagon like peptide ( GLP ) 1 promotes beta cell proliferation and survival through stimulation of its specific G protein coupled receptor ; however , the potential for GLP 1 receptor ( GLP 1R ) agonists to promote growth and proliferation of human pancreatic derived cells remains poorly understood . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Furthermore , GLP 1 receptor knockout mice ( GLP 1R ( / ) ) were completely insensitive to the antidiabetic actions of OFS . ^^^ To determine the importance of GLP 1 receptor dependent mechanisms for the actions of OFS , we studied high fat fed diabetic mice treated with OFS for 4 weeks in the presence or absence of the GLP 1 receptor antagonist exendin 9 39 ( Ex 9 ) . ^^^ In summary , our data show that the antidiabetic actions of OFS require a functional GLP 1 receptor . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
GLP 1R agonists , as well as enzyme inhibitors that prevent GLP 1 degradation , are in late stage clinical trials for the treatment of type 2 diabetes . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
GLP 1 binding and GLP 1 receptor mRNA expression were observed in both astrocytes and microglia . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
Exendin 4 , a GLP 1 receptor agonist first isolated from the venom of the Gila monster Heloderma suspectum , is a clinically valuable , long acting incretin and the skins of several species of frogs synthesize potent insulin releasing peptides with therapeutic potential . . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
GLP 1 receptor activation also augments insulin biosynthesis , restores beta cell sensitivity to glucose , increases beta cell proliferation , and reduces apoptosis , leading to expansion of the beta cell mass . ^^^ A GLP 1 receptor agonist , exendin 4 , has recently been approved for the treatment of type 2 diabetes in the US . ^^^
Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P01275 and P43220	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.68613856
A series of analogs of glucagon like peptide 1 ( GLP 1 ) was made replacing each amino acid with L alanine to identify side chain functional groups required for interaction with the GLP 1 receptor . 0.68613856^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.59973416
Less is known about how the glucagon receptor distinguishes between glucagon and GLP 1 . ( 2 ) We analysed chimeric glucagon / GLP 1 peptides for their ability to bind and activate the glucagon receptor , the GLP 1 receptor and chimeric glucagon / GLP 1 receptors . 0.59973416^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Glucagon like peptide 1 receptor ( GLP 1 R ) mRNA in the rat hypothalamus . ^^^ To date , little is known about the distribution of GLP 1 R and its mRNA in the rodent hypothalamus . ^^^ The purpose of the present study was to utilize in situ hybridization histochemistry to determine the anatomical distribution of GLP 1 R mRNA in the rat hypothalamus . ^^^ The results of these studies revealed an extensive distribution of GLP 1 R mRNA throughout the rostral caudal extent of the hypothalamus ; with a dense accumulation of labeled cells in the supraoptic , paraventricular , and arcuate nuclei . ^^^ The results of these in situ hybridization histochemical studies have provided detailed and novel information about the distribution of GLP 1 R mRNA in the rat hypothalamus . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
We demonstrate here a gene dosage effect for the incretin action of GLP 1 , as heterozygous GLP 1R + / mice exhibit an abnormal glycemic response to oral glucose challenge in association with reduced circulating levels of glucose stimulated insulin . ^^^ In contrast , GLP 1 signaling is not required for normal control of fasting and postabsorptive glucagon levels , and no significant changes were detected in the tissue content of pancreatic and intestinal proglucagon mRNA , glucagon like immunoreactivity , or GLP 1 in GLP 1R / or + / mice . ^^^ Despite the demonstration that GLP 1 stimulates proinsulin gene transcription , pancreatic insulin mRNA transcripts were similar in wild type and GLP 1R / mice . ^^^ Furthermore , despite suggestions that GLP 1 regulates peripheral glucose disposal , whole body glucose utilization was similar in wild type and GLP 1R / mice under both basal and hyperinsulinemic conditions . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Despite the inhibitory effects of GLP 1 on food intake , 6 to 8 week old GLP 1 receptor / ( GLP 1R / ) mice were not obese and did not exhibit disturbances of feeding behavior . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Despite the physiological importance of the enteroinsular axis , disruption of glucagon like peptide ( GLP ) 1 action is associated with only modest glucose intolerance in GLP 1 receptor / ( GLP 1R / ) mice . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The GLP 1 receptor ( GLP 1R ) mediates the insulinotropic effects of the incretion hormone glucagon like peptide 1 ( 7 36 ) amide ( GLP 1 ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Glucagon like peptide 1 ( GLP 1 ) is derived from the peptide precursor pre pro glucagon ( PPG ) by enzymatic cleavage and acts via its receptor , glucagon like peptide 1 receptor ( GLP 1R ) . ^^^ These studies , in addition to describing the sites of GLP 1 and GLP 1R synthesis , suggest that the efferent connections from the nucleus of the solitary tract are more widespread than previously reported . ^^^ The widespread distribution of GLP 1R mRNA containing cells strongly suggests that GLP 1 not only functions as a satiety factor but also acts as a neurotransmitter or neuromodulator in anatomically and functionally distinct areas of the central nervous system . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
We have recently reported that isolated islets from mice homozygous for a GLP 1 receptor null mutation ( GLP 1R ( / ) ) exhibit a well preserved insulin secretory response to glucose . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Male GLP 1 receptor knockout ( GLP 1R / ) mice exhibit reduced gonadal weights , and females exhibit a slight delay in the onset of puberty ; however , male and female GLP 1R / animals reproduce successfully and respond appropriately to fluid restriction . ^^^ These findings suggest that although GLP 1R signaling is not essential for development and basal function of the murine hypothalamic pituitary adrenal axis , abrogation of GLP 1 signaling is associated with impairment of the behavioral and neuroendocrine responses to stress . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
To determine the physiological importance of GLP 1 receptor ( GLP 1R ) leptin interactions , we studied islet function and feeding behavior in ob / ob : GLP 1R ( / ) mice . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The effects of the incretin hormone glucagon like peptide 1 ( 7 36 ) amide ( GLP 1 ) are mediated by the GLP 1 receptor ( GLP 1R ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The purified N terminal fragment ( hereafter referred to as NT ) of the GLP 1R produced in either insect ( Sf 9 ) or mammalian ( COS 7 ) cells was shown to bind GLP 1 . ^^^ The GLP 1R NT protein attached to beads bound GLP 1 , but with lower affinity ( inhibitory concentration ( IC ( 50 ) ) : 4 . 5 10 10 ( 7 ) M ) than wild type ( WT ) GLP 1R ( IC ( 50 ) : 5 . 2 10 10 ( 9 ) M ) . ^^^ The low affinity of GLP 1R NT suggested that other receptor domains may contribute to GLP 1 binding . ^^^ GIP ( 1 151 ) / GLP 1R , but not GIP ( 1 222 ) / GLP 1R , exhibited specific GLP 1 binding and GLP 1 induced cAMP production , suggesting that the region encompassing transmembrane ( TM ) domain 1 through to TM 3 was required for binding . ^^^ These studies indicate that the NT domain of the GLP 1R is able to bind GLP 1 , but charged residues concentrated at the distal TM2 / extracellular loop 1 ( EC 1 ) interface ( K 197 , D 198 , K 202 ) and in EC 1 ( D 215 and R 227 ) probably contribute to the binding determinants of the GLP 1R . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In INS 1 cells over expressing the beta cell GLP 1 receptor ( GLP 1 R ) , we have shown , by radioimmune assay and bioassay of conditioned medium , that an autocrine signaling mechanism of hormone action exists whereby self secreted GLP 1 acts as a competence factor in support of insulin gene transcription . ^^^ The GLP 1 R agonist exendin 4 stimulates RIP 1 Luc activity in a glucose dependent manner , an effect mediated by endogenous GLP 1 Rs , and is blocked by the serine / threonine protein kinase inhibitor Ro 31 8220 . ^^^ Over expression of GLP 1 R in transfected INS 1 cells reduces the threshold for exendin 4 agonist action , whereas basal RIP 1 Luc activity increases 2 . 5 fold in the absence of added agonist . ^^^ The increase of basal RIP 1 Luc activity is a consequence of autocrine stimulation by self secreted GLP 1 and is blocked by introduction of ( 1 ) an inactivating W39A mutation in the N terminus ligand binding domain of GLP 1 R or ( 2 ) mutations in the third cytoplasmic loop that prevent G protein coupling . ^^^ No evidence for constitutive ligand independent signaling properties of the GLP 1 R has been obtained . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
High concentrations of glucagon like peptide 1 ( 7 36 ) amide ( GLP 1 ) and its specific receptor ( GLP 1R ) have been found in the rat hypothalamus . ^^^ In this study the actions of GLP 1 and its related peptides , exendin 4 ( GLP 1R agonist ) , exendin ( 9 39 ) ( GLP 1R antagonist ) and GLP 1 ( 9 36 ) amide ( the major GLP 1 metabolite ) on levels of serotonin ( 5 HT ) , 5 hydroxyindolacetic acid ( 5 HIAA ) and amino acids ( Glu , Asp , Gln , Gly , Tyr , Trp , GABA ) in the hypothalamus were investigated . ^^^ GLP 1 ( 9 36 ) amide , a primary metabolite of GLP 1 , appears to act as an endogenous antagonist at the GLP 1R . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Although GLP 1 receptor ( GLP 1R ) agonists are under development for the treatment of diabetes , GLP 1 administration may increase blood pressure and heart rate in vivo . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
However , the exact mechanism by which the GLP 1 receptor ( GLP 1R ) , a member of the G protein coupled receptor ( GPCR ) superfamily , activates the PI 3 kinase signaling pathway to promote beta cell growth remains unknown . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Both GLP 1 receptor and GIP receptor knockout mice ( GLP 1R ( / ) and GIPR ( / ) , respectively ) have been generated to investigate the physiological importance of this axis . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
We examined beta cell mass regeneration after 70 % Ppx in mice receiving the GLP 1 antagonist Ex 9 39 and in GLP 1R ( / ) mice . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The CJC 1131 albumin conjugate bound to the GLP 1 receptor ( GLP 1R ) and activated cAMP formation in heterologous fibroblasts expressing a GLP 1R . ^^^ These findings demonstrate that an albumin conjugated DAC : GLP 1 mimics the action of native GLP 1 and represents a new approach for prolonged activation of GLP 1R signaling . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
It is secreted primarily in two forms , GLP 1 ( 7 37 ) and GLP 1 ( 7 36 ) NH ( 2 ) , both of which bind to a specific GLP 1 receptor ( GLP 1r ) on the pancreatic beta cell and augment glucose stimulated insulin secretion . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Both intravenous and intracerebroventricular administration of GLP 1 receptor ( GLP 1R ) agonists increase blood pressure and heart rate and induce Fos like immunoreactivity ( Fos IR ) in autonomic regulatory sites in the rat brain . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Glucagon like peptide 1 ( GLP 1 ) acts via its G protein coupled receptor ( GLP 1R ) to regulate blood glucose . ^^^ Although the GLP 1R is widely expressed in peripheral tissues , including the heart , and exogenous GLP 1 administration increases heart rate and blood pressure in rodents , the physiological importance of GLP 1R action in the cardiovascular system remains unclear . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
We found that removing these AAs from Ex 4 to produce Ex ( 1 30 ) reduced the affinity for the GLP 1 receptor ( GLP 1R ) relative to Ex 4 ( IC 50 : Ex 4 , 3 . 22+ / 0 . 9 nM ; Ex ( 1 30 ) , 32+ / 5 . 8 nM ) but made it comparable to that of GLP 1 ( IC 50 : 44 . 9+ / 3 . 2 nM ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The GLP 1 receptor ( GLP 1R ) antagonist Ex ( 9 39 ) did not significantly affect ACTH , aldosterone and cortico sterone responses to Ex 4 . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Glucagon like peptide 1 ( GLP 1 ) is a gut peptide that , together with its receptor , GLP 1R , is expressed in the brain . ^^^ Here we show that intracerebroventricular ( i . c . v . ) GLP 1 and [ Ser ( 2 ) ] exendin ( 1 9 ) ( HSEGTFTSD ; homologous to a conserved domain in the glucagon / GLP 1 family ) enhance associative and spatial learning through GLP 1R . [ Ser ( 2 ) ] exendin ( 1 9 ) , but not GLP 1 , is also active when administered peripherally . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
RESULTS : OXM activates signaling pathways in cells through glucagon or GLP 1 receptors ( GLP 1R ) but transiently inhibits food intake in vivo exclusively through the GLP 1R . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
We report that Albugon , a human glucagon like peptide ( GLP ) 1 albumin recombinant protein , activates GLP 1 receptor ( GLP 1R ) dependent cAMP formation in BHK GLP 1R cells , albeit with a reduced half maximal concentration ( EC ( 50 ) ) ( 0 . 2 vs . 20 nmol / l ) relative to the GLP 1R agonist exendin 4 . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
To address the possibility that the partial disruption of Glucagon like peptide 1 ( GLP 1 ) signaling could cause diabetes , we tried to detect the mutation in GLP 1 receptor ( GLP 1R ) gene in the population with type 2 diabetes . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Most compellingly , pharmacological antagonists of the GLP 1 receptor ( GLP 1R ) block several effects of LiCl in rat . ^^^ The major goal of these experiments was to further test the hypothesis that the central nervous system GLP 1 system is critical to the visceral illness actions of LiCl by using mice with a targeted disruption of the only described GLP 1R . ^^^ Although lateral ventricular GLP 1 produced a CTA in wild type mice , it did not produce a CTA in GLP 1R / mice . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Attenuation of lipopolysaccharide anorexia by antagonism of caudal brain stem but not forebrain GLP 1 R . ^^^ Here we explore GLP 1 mediation of the anorexic response to administration of systemic LPS and address the relative importance of caudal brain stem and forebrain GLP 1 receptor ( GLP 1 R ) for the mediation of the response . ^^^ Fourth intracerebroventricular delivery of the GLP 1 R antagonist exendin ( 9 39 ) ( 10 microg ) did not itself affect food intake in the 24 h after injection but significantly attenuated the otherwise robust ( approximately 60 % ) reduction in food intake obtained after LPS ( 100 microg / kg ) treatment . ^^^ This result highlights a role for caudal brain stem GLP 1 R in the mediation of LPS anorexia but does not rule out the possibility that forebrain receptors also contribute to the response . ^^^ Forebrain contribution was addressed by delivery of the GLP 1 R antagonist to the third ventricle with the caudal flow of cerebrospinal fluid blocked by occlusion of the cerebral aqueduct . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Chronic exposure to GLP 1R agonists promotes homologous GLP 1 receptor desensitization in vitro but does not attenuate GLP 1R dependent glucose homeostasis in vivo . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Coexpression of the CaSR and GLP 1 receptor ( GLP 1R ) produces a pertussis toxin sensitive inhibition of GLP 1 induced cAMP production in response to elevated extracellular [ Ca2+ ] . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
However , native GLP 1 is rapidly degraded by DPP 4 after parenteral administration ; hence , degradation resistant , long acting GLP 1 receptor ( GLP 1R ) agonists are preferable agents for the chronic treatment of human diabetes . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
We determined the role of the islet beta cell and the pancreatic duodenal homeobox 1 ( Pdx 1 ) transcription factor for GLP 1 receptor ( GLP 1R ) dependent actions through analysis of mice with beta cell specific inactivation of the Pdx 1 gene ( beta cell ( Pdx 1 / ) mice ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
A GLP 1R antagonist significantly reduced insulin secretion / production in beta TC 6 insulinoma cells and isolated rat islets , suggesting a functionally important loop between locally produced GLP 1 and its cognate receptor . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Specific binding of 125I GLP 1 ( 7 36 ) amide to the GLP 1R was detected in several brain areas and was inhibited by unlabelled GLP 1 ( 7 36 ) amide , exendin 4 and exendin ( 9 39 ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In addition , induction of Pdx 1 suppressed the expression of glucagon like peptide 1 receptor ( GLP 1R ) , which resulted in marked reduction of both basal and GLP 1 agonist exendin 4 stimulated cellular cAMP levels . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Finally , we provided results to suggest that the transdifferentiated cells are functional by detecting : ( 1 ) functional markers for pancreatic beta cells including prohormone convertase 1 / 3 ( PC1 / 3 ) , insulin C peptide and glucagon like peptide 1 receptor ( GLP 1R ) , ( 2 ) increased insulin mRNA expression after treatment of cells with GLP 1 and betacellulin , physiological stimuli that regulate pancreatic function and ( 3 ) elevated insulin secretion after glucose challenge . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
We previously reported that GLP 1 and exendin 4 , a naturally occurring , long acting analogue of GLP 1 that binds the GLP 1 receptor ( GLP 1R ) , possess neurotrophic properties . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
A GLP 1 receptor ( GLP 1R ) polymorphism in which threonine 149 is substituted with a methionine residue has been recently identified in a patient with type 2 diabetes but was not found in non diabetic control subjects . ^^^ Compared to the wild type receptor , the variant GLP 1R showed ( 1 ) similar expression levels , ( 2 ) 60 and 5 fold reduced binding affinities , respectively , for two GLP 1R full agonists , GLP 1 and exendin 4 , and ( 3 ) markedly decreased potencies of these peptides in triggering cAMP mediated signaling ( despite conserved efficacies ) . ^^^ In contrast to full agonists , the efficacy of the primary GLP 1 metabolite / GLP 1R partial agonist , GLP 1 ( 9 36 ) amide , was essentially abolished by the T149M substitution . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Acetaminophen concentrations , an indirect measurement of gastric emptying rate , were inversely correlated with total ghrelin concentrations ( saline r = 0 . 76 ; 95 % CI = 0 . 90 , 0 . 49 , GLP 1 r = 0 . 47 ; 95 % CI = 0 . 76 , 0 . 04 ) . ^^^ Ghrelin concentrations were only weakly correlated with insulin concentrations ( saline r = 0 . 36 ; 95 % CI = 0 . 69 , 0 . 09 ; GLP 1 r = 0 . 42 ; 95 % CI = 0 . 73 , 0 . 03 ) , but strongly inversely correlated with GIP concentrations ( saline r = 0 . 74 ; 95 % CI= 0 . 89 , 0 . 45 ; GLP 1 r = 0 . 63 ; 95 % CI = 0 . 84 , 0 . 27 ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The insulinotrophic effects of glucagon like peptide 1 ( GLP 1 ) are mediated by its seven transmembrane receptor ( GLP 1R ) in pancreatic beta cells . ^^^ Rapid ( 5 min ) stimulation of cAMP production was observed with 100 nM GLP 1 , 24 h after transfection of 2 microg GLP 1R DNA . ^^^ AtT 20 cells co transfected with GLP 1R and human glycoprotein hormone alpha subunit or rat POMC promoters revealed GLP 1 stimulated cAMP activation of transcription . ^^^ Co transfection of the pIRES vector with the GLP 1R resulted in GLP 1 stimulated activation of POMC promoter driven preproinsulin gene transcription but insulin secretion was not detected . ^^^ However , using an adenoviral expression system to infect AtT 20 cells with GLP 1R and the preproinsulin gene ( including 120 bp of its own promoter ) resulted in a 6 . 4 + / 0 . 6 fold increase in cAMP and a 4 . 9 + / 0 . 8 fold increase in insulin secretion in response to 100 nM GLP 1 . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Glucagon like peptide ( GLP ) 1 promotes beta cell proliferation and survival through stimulation of its specific G protein coupled receptor ; however , the potential for GLP 1 receptor ( GLP 1R ) agonists to promote growth and proliferation of human pancreatic derived cells remains poorly understood . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Furthermore , GLP 1 receptor knockout mice ( GLP 1R ( / ) ) were completely insensitive to the antidiabetic actions of OFS . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
GLP 1R agonists , as well as enzyme inhibitors that prevent GLP 1 degradation , are in late stage clinical trials for the treatment of type 2 diabetes . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
A cDNA for the GLP 1 receptor was isolated by transient expression of a rat pancreatic islet cDNA library into COS cells ; this was followed by binding of radiolabeled GLP 1 and screening by photographic emulsion autoradiography . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The present study examined the internalization and degradation of the GLP 1 receptor complex . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Signal transduction of the GLP 1 receptor cloned from a human insulinoma . ^^^ This study demonstrates the molecular cloning of a cDNA for the GLP 1 receptor from a human insulinoma employing a lambda gt 11 cDNA library . ^^^ The cloned cDNA encoded a seven transmembrane domain protein of 463 amino acids which showed high homology to the GLP 1 receptor in normal human pancreas . ^^^ The understanding of GLP 1 receptor regulation and signal transduction will aid in the discovery of compounds that act as agonists of the GLP 1 receptor for potential use in the treatment of diabetes and will facilitate the understanding of its expression under normal and pathophysiological conditions . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Substitutions in the NH 2 terminal part of the glucagon molecule with the corresponding GLP 1 residues , as for example in [ Ala 2 , Glu 3 ] glucagon and [ Val 10 , Ser 12 ] glucagon , reduced the binding affinity for the glucagon receptor several hundred fold without increasing the affinity for the GLP 1 receptor . ^^^ In contrast , introduction of GLP 1 residues into the far COOH terminal part of the glucagon molecule , e . g . [ Val 27 , Lys 28 , Gly 29 , Arg 30 ] glucagon , had a minimal effect on recognition of the glucagon receptor , but improved the affinity of the analog for the GLP 1 receptor up to 200 fold . ^^^ Similarly , substitutions in especially the far COOH terminal part of the GLP 1 molecule with the corresponding glucagon residues , e . g . des Arg 30 [ Met 27 , Asn 28 , Thr 29 ] GLP 1 , decreased the affinity for the GLP 1 receptor several hundred fold ( IC 50 = 0 . 4 190 nM ) without increasing the affinity for the glucagon receptor . ^^^ Conversely , substitutions in the NH 2 terminal part of the GLP 1 molecule impaired the affinity for the GLP 1 receptor only moderately . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Since the sensitivity of the endocrine pancreas to regulatory hormones can be influenced by their receptor number , we have examined the regulation of glucagon receptor and GLP 1 receptor messenger RNA ( mRNA ) expression in cultured rat pancreatic islets by various factors , including glucose , cAMP , and glucocorticoids . ^^^ By ribonuclease protection assay we have demonstrated the expression of both glucagon and GLP 1 receptor mRNA in cultured rat islets . ^^^ GLP 1 receptor mRNA levels , on the other hand , were not affected by culturing the islets in low glucose concentrations ; however , a small , but significant , decrease in GLP 1 receptor mRNA levels was detected when islets were cultured in 20 mM glucose . ^^^ GLP 1 receptor mRNA levels remained unchanged under all conditions that altered intracellular cAMP levels . ^^^ Finally , in islets cultured in the presence of 10 nM dexamethasone an approximately 50 % decrease in both glucagon and GLP 1 receptor mRNA expression was observed . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Here we studied agonist induced GLP 1 receptor internalization in receptor transfected Chinese hamster lung fibroblasts using three different approaches . ^^^ Thirdly , continuous exposure of GLP 1 receptor expressing cells to iodinated GLP 1 led to a linear accumulation of peptide degradation products in the medium following a lag time of 20 30 min , indicating a continuous cycling of the receptor between the plasma membrane and endosomal compartments . ^^^ Potassium depletion and hypertonicity inhibited transferrin endocytosis , a process known to occur via coated pit formation , as well as GLP 1 receptor endocytosis . ^^^ Surface re expression following one round of GLP 1 receptor endocytosis occurred with a half time of about 15 min . ^^^ Together our data demonstrate that the GLP 1 receptor is internalized upon agonist binding by a route similar to that taken by single transmembrane segment receptors . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Surprisingly , exendin ( 9 39 ) [ Ex ( 9 39 ) ] , a GLP 1 receptor antagonist , and Ex 4 ( 1 39 ) , a GLP 1 receptor agonist , demonstrated some affinity for the GIP receptor , with 39 % and 21 % displacement of [ 125I ] spGIP , respectively , at 1 microM . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Since glucagon like peptide 1 ( 7 36 ) amide ( 7 37 ) ( GLP 1 ) has been found to be a potent insulinotropic hormone , it has been postulated that glucagon stimulates insulin secretion from islet beta cells through the GLP 1 receptor . ^^^ We therefore examined the effects of a GLP 1 receptor antagonist , exendin ( 9 39 ) amide , on glucagon or GLP 1 stimulated insulin release from isolated perfused rat pancreas . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Molecular cloning of a cDNA encoding for the GLP 1 receptor expressed in rat lung . ^^^ This receptor has different biochemical features than the GLP 1 receptor in endocrine pancreas . ^^^ A cDNA library from rat lung in a lambda gt 11 vector was screened with a cDNA probe coding for the rat pancreas GLP 1 receptor . ^^^ Thereby , we found a lung GLP 1 receptor cDNA which shows nearly complete homology to the pancreatic beta cell receptor cDNA . ^^^ Expression of the recombinant lung GLP 1 receptor cDNA in CHO cells displayed a pharmacological profile similar to that seen with cells expressing the beta cell derived cDNA . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
This study uses exendin ( 9 39 ) amide as a GLP 1 receptor antagonist to evaluate the contribution of GLP 1 to the incretin effect . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The discovery of exendin ( 9 39 ) , a GLP 1 receptor antagonist , allowed this to be further investigated . ^^^ The IC 50 for GLP 1 receptor binding , using RIN 5AH beta cell membranes , was found to be 0 . 36 nmol / l for GLP 1 and 3 . 44 nmol / l for exendin ( 9 39 ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The incretin effect of GLP 1 is preserved in patients with Type 2 diabetes mellitus ( NIDDM ) , suggesting that GLP 1 receptor agonist can be used therapeutically in this group of patients . ^^^ To investigate this issue we examined the tissue distribution of GLP 1 receptor using RNAse protection assay in order to avoid the cross reactivities with structurally related receptors and to increase the sensitivity of detection . ^^^ The riboprobe was synthesized from the human pancreatic GLP 1 receptor cDNA and used in hybridization experiments with total RNA isolated from different human tissues . ^^^ In addition to the pancreas , we found expression of GLP 1 receptor mRNA in lung , brain , kidney , stomach and heart . ^^^ Peripheral tissues which are the major sites of glucose turnover , such as liver , skeletal muscle and adipose did not express the pancreatic form of the GLP 1 receptor . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Besides the highly selective GLP 1 receptor , PACAP receptors of types 1 and 2 were present on the cell line and coupled to adenylate cyclase . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Stable expression of the rat GLP 1 receptor in CHO cells : activation and binding characteristics utilizing GLP 1 ( 7 36 ) amide , oxyntomodulin , exendin 4 , and exendin ( 9 39 ) . ^^^ In the present study we stably expressed the rat B cell GLP 1 receptor in CHO cells and studied binding characteristics and receptor activation utilizing the naturally occurring receptor agonist GLP 1 ( 7 36 ) amide ( GLP 1 ) , the proglucagon derived GLP 1 related peptide oxyntomodulin , the GLP 1 receptor agonist exendin 4 , and the specific antagonist exendin ( 9 39 ) . ^^^ This study shows that GLP 1 and exendin 4 are potent agonists at the transfected rat B cell GLP 1 receptor whereas oxyntomodulin is only a weak GLP 1 receptor agonist . ^^^ Furthermore , exendin ( 9 39 ) is a potent GLP 1 receptor antagonist . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Glycosylation of the GLP 1 receptor is a prerequisite for regular receptor function . ^^^ The GLP 1 receptor on RINm5F cells is a glycoprotein with a M ( r ) of 63 , 000 . ^^^ Treatment of the receptor with glycopeptidase F generated a protein with a M ( r ) of 51 , 000 , indicating that the GLP 1 receptor contains N linked glycans . ^^^ Tunicamycin exerted no effect on the GLP 1 receptor mRNA expression . ^^^ Our data show that glycosylation of the GLP 1 receptor is a precondition for regular receptor function . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In addition to the presence of GLP 1 receptor in pancreas we found messenger RNA for this receptor in brain , kidney , heart , fat , skeletal muscle , liver , and intestine . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The GLP 1 receptor is a candidate gene for diabetes mellitus , as mutations may induce the impaired insulin response that is a characteristic feature of NIDDM . ^^^ To study the relationship between the GLP 1 receptor gene and NIDDM , linkage of a microsatellite polymorphism flanking the GLP 1 receptor gene with diabetes was investigated in three Caucasian families with MODY and in the nuclear families of 12 NIDDM probands . ^^^ Mutations in or near the GLP 1 receptor gene are unlikely to be the major cause of the inherited predisposition to NIDDM in Caucasian pedigrees , but we can not exclude a role for this locus in a polygenic model or a major role in some pedigrees . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Using these markers , role of GLP 1 receptor mutations in the pathogenesis of NIDDM was studied . ^^^ Linkage was rejected between the GLP 1 receptor gene and NIDDM in Caucasian late onset NIDDM families and in French MODY families . ^^^ Mutations in the GLP 1 receptor gene do not appear to be major genetic determinants of NIDDM . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Ligand specificity of the rat GLP 1 receptor recombinantly expressed in Chinese hamster ovary ( CHO ) cells . ^^^ This study was designed to precisely characterize the binding behavior and activation of the recombinant GLP 1 receptor against naturally occurring ligands of the glucagon / VIP / secretin peptide hormone family . ^^^ CHO cells were stably transfected with a plasmid containing a cDNA encoding for the rat GLP 1 receptor . ^^^ This data shows that the GLP 1 receptor is characterized by a high ligand specificity . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The molecular weight of this apparent GLP 1 receptor in human endocrine pancreatic tissue was of identical size as the GLP 1 receptor on rat insulinoma derived RINm5F cell membranes . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
It is proposed that at least one factor contributing to the pathogenesis of NIDDM is a desensitization of the GLP 1 receptor on beta cells induced by the hypersecretion of GLP 1 . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In contrast , mRNA transcripts for the GLP 1 receptor were detected in both small and large intestine as well as in pancreas , liver , lung , and kidney . ^^^ Both glucagon and GLP 1 receptor mRNA transcripts were identified in different regions of the fetal and adult mouse brain , but the relative levels of GLP 1 receptor mRNA transcripts were much greater in the central nervous system . ^^^ Furthermore , regulation of the GLP 1 receptor ( but not the glucagon receptor ) gene in the brain resembled the pattern of region specific gene expression recently defined for the mouse proglucagon gene . ^^^ Taken together , these studies define novel sites for both glucagon and GLP 1 receptor gene expression in the mouse and suggest that different regulatory mechanisms have evolved for tissue specific and developmental control of receptor gene expression . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Here we studied the coupling of the cloned GLP 1 receptor , expressed in fibroblasts or in COS cells , to intracellular second messengers and compared this signaling with that of the endogenous receptor expressed in insulinoma cell lines . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The hypothesis to be tested in this study was that defects in the islet beta cell GLP 1 receptor gene contribute to the impaired glucose regulated insulin secretion of non insulin dependent diabetes mellitus ( NIDDM ) . ^^^ Human islet GLP 1 receptor genomic clones were isolated , and two highly polymorphic simple sequence repeat regions ( GLP 1R CA 1 and GLP 1R CA 3 ) were identified . ^^^ By genotyping all members of the 40 reference Centre d ' Etude du Polymorphisme Humain pedigrees at GLP 1R CA 3 , the human GLP 1 receptor gene was uniquely placed on chromosome 6p between GLO 1 and D6S19 , 20 . 4 cM from human leukocyte antigen . ^^^ To assess the possible role of the GLP 1 receptor gene in determining the genetic susceptibility to NIDDM , allelic frequencies of GLP 1R CA 1 and GLP 1R CA 3 were compared between African American NIDDM patients ( n = 95 ) and control subjects ( n = 93 ) . ^^^ The GLP 1 receptor gene simple sequence repeat polymorphisms were used for linkage analysis in Utah Mormon pedigrees ( n = 16 ) with NIDDM . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Transfection of the human GLP 1 receptor into COS 7 cells confers upon them high affinity binding for [ 125I ] GLP 1 ( 7 36 ) amide . ^^^ In membranes prepared from COS 7 cells transfected with the human GLP 1 receptor , the binding of [ 125I ] GLP 1 ( 7 36 ) amide is inhibited with the rank order of potency GLP 1 ( 7 36 ) amide > glucagon > secretin , characteristic of a GLP 1 receptor . ^^^ The human GLP 1 receptor is functionally coupled to increases in intracellular cAMP in these cells : incubation of COS 7 cells expressing the human GLP 1 receptor with GLP 1 ( 7 36 ) amide gives rise to a 4 fold increase in cyclic AMP over basal levels , with an EC 50 of 25pM . ^^^ Glucagon is also a full agonist but is 200 fold less potent than GLP 1 ( 7 36 ) amide in stimulating the human GLP 1 receptor . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Isolation and sequencing of cDNA of the GLP 1 receptor ] . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
This study establishes that a single GLP 1 receptor species can mediate the effects of GLP 1 ( 7 37 ) through multiple G protein coupled signaling pathways , including the adenylyl cyclase system , phospholipase C , and changes in [ Ca2+ ] i . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The biological actions of GLP 1 are mediated by the GLP 1 receptor , the structure of which has recently been determined . ^^^ Defects in insulin secretion are a common feature of NIDDM and as such the GLP 1 receptor is a candidate for contributing to the development of this clinically and genetically heterogeneous disorder . ^^^ As a first step in determining the role of the GLP 1 receptor in the development of NIDDM , we have isolated the human GLP 1 receptor gene and mapped it to chromosome 6 , band p21 . 1 , using the technique of fluorescence in situ hybridization . ^^^ We also identified a simple tandem repeat DNA polymorphism in the human GLP 1 receptor gene of the form ( TG ) n . ^^^ We have used this DNA polymorphism to localize the GLP 1 receptor gene within the genetic map of the short arm of chromosome 6 . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
We demonstrate that exendin 4 and truncated exendin ( 9 39 ) amide specifically interact with the GLP 1 receptor on insulinoma derived cells and on lung membranes . ^^^ In conclusion , exendin 4 is an agonist and exendin ( 9 39 ) amide is a specific GLP 1 receptor antagonist . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
To determine the structure and coupling mechanisms of the human GLP 1 receptor we have isolated two pancreatic islet cDNAs , encoding the 463 amino acid receptor and differing mainly in their 3 ' untranslated regions . ^^^ The deduced amino acid sequence is 90 % homologous with the rat GLP 1 receptor . ^^^ Thus , like the structurally related glucagon and parathyroid hormone receptors , the human GLP 1 receptor can activate multiple intracellular signaling pathways including adenylyl cyclase and PLC . ^^^ Knowledge of the GLP 1 receptor structure will facilitate the development of receptor agonists and elucidation of the important role of GLP 1 in normal physiology and disease states . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Cloning and functional expression of the human islet GLP 1 receptor . ^^^ Two peptides from the venom of the lizard Heloderma suspectum , exendin 4 and exendin ( 9 39 ) , displayed similar ligand binding affinities to the human GLP 1 receptor . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Binding studies with [ 125I ] [ Tyr 39 ] exendin 4 , a GLP 1 receptor agonist , showed an identical distribution pattern of binding sites . ^^^ In conclusion , the biochemical data support the idea that the central GLP 1 receptor resembles the peripheral GLP 1 receptor . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
By Northern blot analysis the presence of GLP 1 receptor mRNA was shown in B ( beta TC 1 cells ) and D ( RIN 1048 38 ) cells but not in A ( INR 1 G9 ) cells , thus confirming functional data demonstrating the absence of active GLP 1 receptors on glucagon producing cells . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
A series of chimeric receptors in which 4 6 amino acids in the N terminal extracellular domain of the human GLP 1 receptor were replaced with the analogous region of the human glucagon receptor were constructed and expressed in COS 7 cells . ^^^ Thus , the substitution of as few as four residues of the GLP 1 receptor profoundly affects its selectivity for the homologous peptide agonists GLP 1 and glucagon . ^^^ These results suggest the extracellular N terminal domain of the GLP 1 receptor harbours molecular determinants for both agonist binding affinity and selectivity . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In this study , we examined the tissue distribution of GLP 1 receptor ( GLP lR ) messenger RNA ( mRNA ) in rat by RNAse protection , RT PCR , and in situ hybridization . ^^^ These results indicate that sequences corresponding to the cloned rat islet GLP 1 receptor are expressed in the pancreatic islets , lung , hypothalamus , stomach , heart , and kidney but not in adipose , liver , and skeletal muscle . ^^^ Further , the GLP 1 receptor expressed in the kidney and heart may be structural variants of the known receptor . ^^^ Therefore , the observed extrapancreatic actions of GLP 1 may not be strictly confined to interactions with the defined GLP 1 receptor . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The binding affinity to the GLP 1 receptor was found to be sensitive to GIP like exchanges in the N terminal 22 amino acids as well as in positions 13 and 15 ( loss of affinity 280 fold to more than 1000 fold ) . ^^^ C terminal substitution of the GLP 1 sequence by GIP diminished the affinity towards the GLP 1 receptor only 20 fold . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Exchange of W 39 by A within the N terminal extracellular domain of the GLP 1 receptor results in a loss of receptor function . ^^^ The GLP 1 receptor belongs to a new subfamily of the superfamily of seven transmembrane , G protein coupled receptors ( 7 TM receptors ) . ^^^ We show that a single point mutation within a nonconserved motif of the N terminal , extracellular domain of the GLP 1 receptor results in a dramatic impairment of receptor function . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Down regulation of the GLP 1 receptor mRNA was observed after exposure of CA 77 C cells with GLP 1 ( 7 37 ) . ^^^ GLP 1 ( 7 37 ) increased cAMP formation in CA 77 cells in a dose dependent manner ; exendin ( 9 39 ) , a GLP 1 receptor antagonist , inhibited cAMP production . ^^^ The GLP 1 peptide which is produced by intestinal cells could be involved in the control of CT secretion through an entero thyroidal axis implying GLP 1 receptor and increased CT gene expression . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The specific GLP 1 receptor agonists , exendin 4 and exendin 3 , and the antagonist , exendin ( 9 39 ) , bound to the receptor sites with high affinity ( Ki = 190 + / 70 pM ; 130 + / 50 and 1200 + / 470 pM , respectively ) . ^^^ Chemical cross linking of [ 125I ] GLP 1 receptor complexes revealed a single band of 64 , 300 + / 100 Mr in alpha TSH membranes . ^^^ In addition , specific PCR studies demonstrated the presence of GLP 1 receptor messenger RNA . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Internalization of the GLP 1 receptor did not participate in the desensitization induced by PMA , as a mutant GLP 1 receptor lacking the last 20 amino acids of the cytoplasmic tail was found to be totally resistant to the internalization process , but was still desensitized after PMA preexposure . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Colocalization of glucagon like peptide 1 ( GLP 1 ) receptors , glucose transporter GLUT 2 , and glucokinase mRNAs in rat hypothalamic cells : evidence for a role of GLP 1 receptor agonists as an inhibitory signal for food and water intake . ^^^ This hypothesis was confirmed by analyzing the effects of both systemic and central administration of GLP 1 receptor ligands . ^^^ Pretreatment with an i . c . v . dose of a GLP 1 receptor antagonist [ exendin ( 9 39 ) ; 2 , 500 ng ] reversed the inhibitory effects of GLP 1 ( 7 36 ) amide ( 1 , 000 ng dose ) and exendin 4 ( 25 ng dose ) on food and water ingestion . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The GLP 1 receptor belongs to the family of seven transmembrane domain receptors coupled to G proteins . ^^^ We have analyzed the regulation of GLP 1 receptor function and expression by its own ligand and the cAMP dependent pathway in rat insulinoma derived beta cells ( RINm5F ) . ^^^ The GLP 1 receptor underwent rapid homologous desensitization , which occurred at the receptor level . ^^^ GLP 1 receptor mRNA levels were down regulated during incubation of cells by agents increasing cAMP levels including GLP 1 itself . ^^^ Forskolin , the PKA activator 5 , 6 dichloro 1 beta D ribofuranosyl benzimidazole 3 , 5 monophosphorothiotate , and GLP 1 stabilized the GLP 1 receptor mRNA . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
To ascertain the relative physiological importance of GLP 1 as a regulator of feeding behavior and insulin secretion , we have generated mice with a targeted disruption of the GLP 1 receptor gene ( GLP1R ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The GLP 1 receptor belongs to the family of seven transmembrane domain receptors . ^^^ TPA induced significantly lower GLP 1 receptor mRNA levels under steady state conditions after 6 and 24 h . ^^^ The stability of the GLP 1 receptor mRNA was unchanged . ^^^ These data indicate that PKC activation downregulates the expression of the GLP 1 receptor gene , mainly at the transcriptional level . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
It is , however , unknown whether oxyntomodulin and GLP 2 elicit a biological response by interacting with the GLP 1 receptor . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The GLP 1 receptor is presently attracting much attention , since it is the target protein of the antidiabetic gut hormone GLP 1 . ^^^ To establish the functional significance of the N terminal part of the GLP 1 receptor for ligand binding , the extracellular domain was isolated and purified . ^^^ Utilizing CHL cells expressing the cloned GLP 1 receptor , we demonstrate that the isolated , solubilized N terminal part of the receptor protein competes for GLP 1 binding with the intact wild type receptor . ^^^ These data underline the significance of the N terminal domain of the GLP 1 receptor for ligand binding . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
ICV injection of the specific GLP 1 receptor antagonist , exendin ( 9 39 ) , blocked the inhibitory effect of GLP 1 on food intake . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Roles of the RAM and ANK domains in signaling by the C . elegans GLP 1 receptor . ^^^ In Caenorhabditis elegans , the GLP 1 receptor acts with a downstream transcriptional regulator , LAG 1 , to mediate intercellular signaling . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Receptor binding studies using baby hamster kidney cells expressing the human pancreatic GLP 1 receptor showed that the affinity of GLP 1 ( 9 36 ) amide , GLP 1 ( 7 35 ) and GLP 1 ( 7 34 ) was 0 . 95 % , 12 % and 2 . 8 % , respectively , of the affinity of GLP 1 ( 7 36 ) amide . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
A lizard glucagon like peptide 1 ( GLP 1 ) related peptide , exendin 4 , binds to the GLP 1 receptor and mimics the actions of GLP 1 in vivo . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Reciprocal cellular distribution of glucagon like peptide 1 ( GLP 1 ) immunoreactivity and GLP 1 receptor mRNA in pancreatic islets of rat . ^^^ The respective cellular distribution of glucagon like peptide 1 ( GLP 1 ) immunoreactivity and mRNA expression of the GLP 1 receptor was compared in rat pancreas by means of immunohistochemistry and in situ hybridization . ^^^ In contrast , GLP 1 receptor mRNA signals were confined to the central part of pancreatic islets . ^^^ Neither GLP 1 immunoreactivity nor GLP 1 receptor mRNA signals were detected in the exocrine pancreatic acinar cells or duct cells . ^^^ The differential distribution of GLP 1 immunoreactivity and GLP 1 receptor mRNA signals indicates that the GLP 1 amino acid sequence is present in the alpha cell zone of pancreatic islets , whereas the GLP 1 receptor is expressed mainly by beta cells . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The localization of the GLP 1 receptor on insulin and somatostatin producing cells in the islets is well established . ^^^ Whether the GLP 1 receptor also resides on the glucagon producing alpha cells remains controversial and is reported to be absent on rat alpha cells . ^^^ To investigate the distribution of the GLP 1 receptor on islet cells , we examined the expression of GLP 1 receptor mRNA in phenotypically distinct islet cell lines and islets , and the presence of immunoreactive GLP 1 receptor in dispersed rat islet cells using a specific antiserum . ^^^ GLP 1 receptor mRNA was readily detected by reverse transcription polymerase chain reaction ( RT PCR ) in both rat islets and in established islet cell lines representing distinct alpha , beta , and delta cell phenotypes . ^^^ In addition , GLP 1 receptor expression was detected in single rat alpha cells by single cell RT PCR . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Five out of six tryptophan residues in the N terminal extracellular domain of the rat GLP 1 receptor are essential for its ability to bind GLP 1 . ^^^ This indicates the significance of hydrophobic interactions within the N terminal domain of the GLP 1 receptor . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Fluorescein Trp 25 exendin 4 , a biologically active fluorescent probe for the human GLP 1 receptor . ^^^ FLEX is equipotent to GLP 1 ( 7 36 ) amide and exendin 4 as an inhibitor of [ 125I ] GLP 1 binding to the human GLP 1 receptor stably expressed in CHO cells , and maintains full biological potency and efficacy as measured by the stimulation of cAMP accumulation in these cells . ^^^ The binding is specific and saturable ( Kd = 2 . 0 + / 0 . 4 nM ) , and GLP 1 ( 7 36 ) amide and exendin 4 are equipotent inhibitors of FLEX binding to the human GLP 1 receptor . ^^^ Thus , FLEX is a potent , biologically active ligand that is useful for the study of the binding and functional characteristics of the human GLP 1 receptor . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Internalization and homologous desensitization of the GLP 1 receptor depend on phosphorylation of the receptor carboxyl tail at the same three sites . ^^^ Homologous desensitization and internalization of the GLP 1 receptor correlate with phosphorylation of the receptor in a 33 amino acid segment of the cytoplasmic tail . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In contrast , expression of GLP 1 receptor gene was detected in brain , pancreas and pancreatic islets but not in liver , kidney , or ileum . ^^^ In the cDNA pool of MIN 6 cells , both glucagon and GLP 1 receptor genes were identified and showed higher expression level in MIN 6 cells cultured under high glucose condition than in those cultured under low glucose condition . ^^^ These results suggest that glucagon and GLP 1 receptor genes are expressed in pancreatic beta cells and their expression is upregulated by glucose . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Cloning and characterization of the 5 ' flanking sequences ( promoter region ) of the human GLP 1 receptor gene . ^^^ To elucidate the tissue specific regulation of the GLP 1 receptor we screened a human genomic library with a human GLP 1 receptor cDNA . ^^^ Transient transfections of GLP 1 receptor producing and non producing cells with promoter / reporter gene constructs revealed that the putative Sp 1 binding sites and several other silencer and tissue specific elements are important for the activity . ^^^ Therefore , 3000 bp upstream the GLP 1 receptor coding sequences comprise regulatory elements essential for the tissue and cell specific transcription of the gene . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In this study , we evaluated the effects of stably transfecting the GLP 1 receptor into an insulinoma cell line , RIN 1046 38 , on basal and glucose mediated insulin secretion and on second messenger pathways involved in insulin secretion . ^^^ The GLP 1 receptor transfected cells had similar insulin mRNA levels but higher insulin content compared with parental cells . ^^^ In GLP 1 receptor transfected cells , glucose ( 0 . 5 mM ) mediated insulin release was increased compared with parental cells ( 4 . 52 + / 0 . 79 pmol insulin / l per mg protein 10 h vs . 2 . 21 + / 0 . 36 pmol insulin / l per mg protein 10 h ; mean + / S . ^^^ By hemolytic plaque assay measuring single cell insulin secretion , we observed that in the GLP 1 receptor transfected cells versus parental cells the increased insulin secretion was due to the presence of more glucose responsive cells as well as more insulin released in response to glucose per cell . ^^^ In response to GLP 1 , both GLP 1 receptor transfected cells and parental cells showed increased cAMP levels independent of glucose . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Unexpectedly , these cDNAs were found to encode three unique glucagon like 1 peptides , termed xenGLP 1A , xenGLP 1B , and xenGLP 1C in addition to the typical proglucagon derived hormones glucagon and GLP 2 . xenGLP 1A , 1B , and 1C were synthesized and tested for their ability to bind and activate the human GLP 1 receptor ( hGLP 1R ) , and to stimulate insulin release from rat pancreas . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The stimulatory action of GLP 1 ( 7 36 ) amide on exocytosis was mimicked by the pancreatic hormone glucagon and exendin 4 , a GLP 1 receptor agonist . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
To analyze the transition from agonist to antagonist and to identify the amino acid residues involved in ligand activation of the GLP 1 receptor , we used exendin analogs with successive N terminal truncations . ^^^ Chinese hamster ovary cells stably transfected with the rat GLP 1 receptor were assayed for changes in intracellular cAMP caused by the test peptides in the absence or presence of half maximal stimulatory doses of GLP 1 . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In addition , an antagonist of pancreatic GLP 1 receptor , exendin 4 ( 9 39 ) , acted as an agonist to decrease cAMP levels in 3T3 L 1 adipocytes as did exendin 4 ( 1 39 ) , a known agonist for the pancreatic GLP 1 receptor . ^^^ Binding studies using 125I GLP 1 also suggest that pancreatic GLP 1 receptor isoform is not responsible for the effect of GLP 1 and related peptides in 3T3 L 1 adipocytes . ^^^ Based on these results , we propose that the major form of the GLP receptor in 3T3 L 1 adipocytes is functionally different from the pancreatic GLP 1 receptor . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
ICV injection of the specific GLP 1 receptor antagonist , exendin ( 9 39 ) , at the onset of dark phase , did not affect feeding in saline pre treated controls , but blocked the reduction in food intake and body weight of leptin pre treated rats . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In gastric fistula rats , vagal afferent denervation and peripheral administration of the GLP 1 receptor antagonist exendin ( 9 39 ) amide enhanced emptying of a glucose meal , whereas intracerebroventricular exendin was ineffective . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
GLP 1 receptor gen `` knock out ' ' causes glucose intolerance , but no alterations of eating behavior ] . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Because leptin reduces food intake but inhibits insulin secretion , we examined leptin action in mice with a null mutation in the GLP 1 receptor . ^^^ Intracerebroventricular leptin administration inhibited food intake in both wild type and GLP 1 receptor ( GLP IR ) / mice , and daily intraperitoneal administration of leptin for 2 weeks produced comparable reductions in food intake and body weight in control and GLP IR / mice . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
It is proposed that at least one factor contributing to the pathogenesis of non insulin dependent diabetes mellitus ( NIDDM ) is desensitization of the GLP 1 receptor on beta cells . ^^^ Agonists of GLP 1 receptor have been proposed as new potential therapeutic agents in NIDDM patients . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Glucagon induced cAMP production in beta cells was inhibited both by 1 micromol / l des His 1 [ Glu 9 ] glucagon amide and exendin ( 9 39 ) amide , a specific GLP 1 receptor antagonist , whereas GLP 1 induced cAMP formation was suppressed only by exendin ( 9 39 ) amide . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
This inhibitory action occurs independent of circulating concentrations of somatostatin and gastrin and appears to involve a GLP 1 receptor distinct from that mediating incretin effects . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
GLP 1 receptor binding and GLP 1 induced cAMP generation remained unchanged . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The specific GLP 1 receptor agonists , exendin 3 and exendin 4 , also showed high affinity ( Ki = 0 . 3+ / 0 . 05 and 0 . 32+ / 0 . 06 nM , respectively ) as did the antagonist exendin ( 9 39 ) ( Ki = 0 . 98+ / 0 . 24 nM ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In vitro functional densensitization of the GLP 1 receptor was not observed after overnight exposure of Rin m5F insulinoma cells to GLP 1 at concentrations up to 10 nM . ^^^ These results indicate that the GLP 1 pathways in the central nervous system controlling food consumption do not desensitize after chronic exposure to GLP 1 and suggest that agonists of the central GLP 1 receptor may be effective agents for the treatment of obesity . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
We conclude that GLP 1 receptor expression in Xenopus oocytes evokes inositol trisphosphate dependent intracellular Ca2+ mobilization independent of the cAMP / PKA signaling pathway . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The observation that mice with homozygous disruption of the GLP 1 receptor gene are diabetic with a diminished incretin response to glucose underlines the first function in vivo . ^^^ Isolated islets of Langerhans from GLP 1 receptor / mice were studied to assess the second function in vitro . ^^^ Absence of pancreatic GLP 1 receptor function was observed in GLP 1 receptor / mice , as exemplified by loss of [ 125I ] GLP 1 binding to pancreatic islets in situ and by the lack of GLP 1 potentiation of glucose induced insulin secretion from perifused islets . ^^^ Acute glucose competence of the beta cells , assessed by perifusing islets with stepwise increases of the medium glucose concentration , was well preserved in GLP 1 receptor / islets in terms of insulin secretion . ^^^ Furthermore , neither islet nor total pancreatic insulin content was significantly changed in the GLP 1 receptor / mice when compared with age and sex matched controls . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
It plays an important role as an incretin hormone ; thus , mice with a null muation in the gene encoding the GLP 1 receptor are glucose intolerant . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Inhibition induced by GLP 1 was reversed by i . v . infusion of GLP 1 receptor antagonist , Exendin ( 9 39 ) ( 3 10 10 ( 8 ) moles / kg per 10 min ) ( n = 6 ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In conclusion , GLP 1 seems to inhibit small bowel motility directly via the GLP 1 receptor . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Tissue distribution of rat glucagon receptor and GLP 1 receptor gene expression . ^^^ This paper highlights the diversity of both GLP 1 and glucagon activity by studying the tissue distribution of glucagon and GLP 1 receptor gene expression by both Southern blot analysis of RT PCR products and nuclease protection assays . ^^^ By Southern blot analysis of RT PCR products , GLP 1 receptor mRNA was detected in lung , hypothalamus , hippocampus , cerebral cortex , kidney , pancreas , and throughout the gastrointestinal tract . ^^^ Nuclease protection assay revealed glucagon receptor expression to be highest in liver and kidney , whereas GLP 1 receptor expression was only detected by protection assay in lung , stomach , and large bowel . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
We therefore determined if third ventricular ( i3vt ) infusion of a GLP 1 receptor antagonist would block LiCl induced c Fos expression in the brainstem . ^^^ Relative to rats pretreated with i3vt infusion of vehicle , pretreatment with the potent GLP 1 receptor antagonist , des His 1 Glu9 exendin 4 ( 10 . 0 microgram ) , significantly attenuated LiCl induced ( 76 mg / kg ; i . p . ) c Fos expression in several brainstem regions , including the area postrema , the nucleus of the solitary tract , and the lateral parabrachial nucleus . ^^^ These results suggest that LiCl induced c Fos expression in the rat brainstem is mediated , at least in part , by GLP 1 receptor signaling . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
GLP 1 action in L 6 myotubes is via a receptor different from the pancreatic GLP 1 receptor . ^^^ The incretin hormone glucagon like peptide 1 ( GLP 1 ) ( 7 36 ) amide is best known for its antidiabetogenic actions mediated via a GLP 1 receptor present on pancreatic endocrine cells . ^^^ In L 6 myotubes transfected with pancreatic GLP 1 receptor , GLP 1 increased cAMP levels and inhibited glycogen synthesis by 60 % . ^^^ An antagonist of pancreatic GLP 1 receptor , exendin 4 ( 9 39 ) , inhibited GLP 1 mediated glycogen synthesis in GLP 1 receptor transfected L 6 myotubes . ^^^ However , in parental L 6 myotubes , exendin 4 ( 9 39 ) and GLP 1 ( 1 36 ) amide , an inactive peptide on pancreatic GLP 1 receptor , displaced 125I labeled GLP 1 binding and stimulated glycogen synthesis by 186 and 130 % , respectively . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In Northern blots , transcripts of 2 . 7 , 3 . 6 and 3 . 7 kb were observed in rat islets and RINm5F cells after hybridization with rat GLP 1 receptor cDNA probes of either 21 9 bp or 1 . 5 kb . ^^^ However , a single 3 . 6 kb transcript was observed in the latter two cases when a human GLP 1 receptor cDNA probe of 1 . 6 kb was used for hybridization . ^^^ The expression of the mRNA for the GLP 1 receptor differs , however , from that found in rat or human islets . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
High level expression of the GLP 1 receptor results in receptor desensitization . ^^^ The GLP 1 receptor is desensitized when expressed in high numbers on the cells . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The genomic organization of the human GLP 1 receptor gene . ^^^ The coding sequence of the GLP 1 receptor is interrupted by 12 introns . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The insulinotropic hormone , glucagon like peptide 1 ( GLP 1 ) , which has been proposed as a new treatment for type 2 diabetes , is metabolized extremely rapidly by the ubiquitous enzyme , dipeptidyl peptidase 4 ( DPP 4 ) , resulting in the formation of a metabolite , which may act as an antagonist at the GLP 1 receptor . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
This latter effect was receptor dependent , as a beta cell line not expressing the GLP 1 receptor was not affected by exendin ( 9 39 ) . ^^^ These data therefore demonstrated that 1 ) exendin ( 9 39 ) is an inverse agonist of the murine GLP 1 receptor ; 2 ) the decreased basal cAMP levels induced by this peptide inhibit the secretory response of betaTC Tet cells and mouse pancreatic islets to glucose ; 3 ) as this effect was observed only with growth arrested cells , this indicates that the mechanism by which cAMP leads to potentiation of insulin secretion is different in proliferating and growth arrested cells ; and 4 ) the presence of the GLP 1 receptor , even in the absence of bound peptide , is important for maintaining elevated intracellular cAMP levels and , therefore , the glucose competence of the beta cells . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Using glucose responsive HIT T 15 cells , [ Ser ] GLP 1 ( 7 36 ) amide showed strong insulinotropic activity , which was inhibited by the specific GLP 1 receptor antagonist exendin 4 ( 9 39 ) amide . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In situ hybridization histochemistry revealed colocalization of the mRNAs for GLP 1 receptor , AVP , and OX in neurons of the hypothalamic supraoptic and paraventricular nuclei . ^^^ The coexpression of GLP 1 receptor and AVP mRNAs in hypothalamic supraoptic and paraventricular nuclei gives further support to the already reported central effects of GLP 1 ( 7 36 ) amide on AVP . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
We here report that repeated intracerebroventricular ( i . c . v . ) injection of GLP 1 or the GLP 1 receptor antagonist , exendin ( 9 39 ) , affects food intake and body weight . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Recently , we cloned the 5 ' region of the GLP 1 receptor gene and found that tissue and cell specificity is lost by 5 ' deletion to 574 . ^^^ Therefore , the basal activity of the GLP 1 receptor gene is mediated by two proximal Sp 1 binding sites , whereas a more distal site acts as a repressor . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Duodenal inhibition induced by intraduodenal ( N = 6 ) or intraileal ( N = 6 ) infusion of ovoalbumin hydrolysate was reversed by intraarterial infusion of GLP 1 receptor antagonist , exendin ( 9 39 ) ( 3 10 10 ( 8 ) mol / kg / 40 min ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Also , GLP 1 receptor cDNA from human and rat brains has been cloned and sequenced , and the deduced amino acid sequences are the same as those found in pancreatic islets . ^^^ Central administration ( icv ) of GLP 1 ( 7 36 ) amide produces a marked reduction in food and water intake , and the colocalization of the GLP 1 receptor , GLUT 2 , and glucokinase mRNAs in hypothalamic neurons involved in glucose sensing suggests that these cells may be involved in the transduction of signals needed to produce a state of fullness . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Chinese hamster ovary ( CHO ) cells stably expressing the human insulin receptor and the rat glucagon like peptide 1 ( GLP 1 ) receptor ( CHO / GLPR ) were used to study the functional coupling of the GLP 1 receptor with G proteins and to examine the regulation of the mitogen activated protein ( MAP ) kinase signaling pathway by GLP 1 . ^^^ We showed that ligand activation of GLP 1 receptor led to increased incorporation of GTP azidoanilide into Gs alpha , Gq / 11 alpha , and Gi 1 , 2 alpha , but not Gi 3 alpha . ^^^ Ligand stimulated GLP 1 receptor produced 1 . 45 and 2 . 7 fold increases in tyrosine phosphorylation of 42 kDa extracellular signal regulated kinase ( ERK ) in CHO / GLPR and RIN 1046 38 cells , respectively . ^^^ Our study indicates a direct coupling between the GLP 1 receptor and several G proteins , and that CTX sensitive proteins are required for GLP 1 mediated activation of MAP kinases . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
GLP 1 receptor binding was investigated in RINm5F cells . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Genes that have been shown to have a regulatory function in the control of body fat utilization , eating behavior , and / or metabolic rate in rodent models of obesity include leptin ( LEP ) , leptin receptor ( LEPR ) , neuropeptide Y ( NPY ) , NPY Y 1 receptor ( NPYY 1 ) , glucagon like peptide 1 ( GLP 1 ) , GLP 1 receptor ( GLP1R ) , and uncoupling protein 1 ( UCP 1 ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
This effect is reproduced by 8 Br cAMP , but is blocked by a GLP 1 receptor antagonist ( exendin ( 9 39 ) ) , a cAMP antagonist ( ( Rp ) cAMPS ) , an L type Ca2+ channel antagonist ( nimodipine ) , an antagonist of the sarco ( endo ) plasmic reticulum Ca2+ ATPase ( thapsigargin ) , or by ryanodine . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
GLP 1 receptor gene expression was found using reverse transcriptase polymerase chain reaction of poly ( A ) selected RNA in muscle and adipose tissue , but not in liver . ^^^ Low levels of GLP 1 receptor gene expression were also found in adipose tissue using Northern blotting . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
TPRA 40 has seven putative transmembrane domains and shows little homology with the known GLP 1 receptor or with other G protein coupled receptors . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Using a peptide analog of GLP 1 , the GLP 1 receptor antagonist exendin ( 9 39 ) , we investigated whether the conjugation of a carbohydrate structure to exendin ( 9 39 ) would generate a peptide with intact biological activity and improved survival in circulation . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Structure of the integral membrane domain of the GLP 1 receptor . ^^^ A three dimensional ( 3D ) model of the integral membrane domain of the GLP 1 receptor , a member of the secretin receptor family of the G protein coupled receptor superfamily is proposed . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Recently , we generated two GLP 1 receptor mutant isoforms ( IC 3 1 and DM 1 ) that displayed efficient ligand binding and the ability to promote Ca2+ mobilization from intracellular stores but lacked the ability to couple to AC . ^^^ In the present study , the wild type rat GLP 1 receptor ( WT GLP 1 R ) or the IC 3 1 and DM 1 mutant forms were expressed for the first time in the insulin producing HIT T 15 cells . ^^^ These studies demonstrate that the GLP 1 receptor efficiently couples to AC to stimulate insulin secretion and that receptors lacking critical residues in the proximal region of the third intracellular loop can effectively uncouple the receptor from cAMP production , VDCC activity , insulin secretion , and insulin biosynthesis . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
A GLP 1 receptor antagonist or GLP 1 antisera have been shown to reduce meal stimulated insulin secretion in animals , suggesting that GLP 1 has a physiological `` incretin ' ' function ( augmentation of postprandial insulin secretion due to intestinal hormones ) for GLP 1 . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Juxtacellular administration of GLP 1 ( 7 36 ) amide first increased and then decreased single unit activities recorded in the hippocampal CA 1 , which effects were antagonized by exendin ( 9 39 ) amide , a GLP 1 receptor antagonist , or 6 cyano 7 nitroquinoxaline 2 , 3 dione , a non NMDA type glutamate receptor antagonist . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
It is an important incretin hormone ; mice with a null mutation in the GLP 1 receptor gene develop glucose intolerance . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In the first experiment , ICV infusion of a GLP 1 receptor antagonist [ exendin 4 ( 3 39 ) ] significantly attenuated ( 10 microgram dose ) or completely blocked ( 20 microgram dose ) the inhibition of food intake produced by subsequent ICV infusion of GLP 1 ( 7 36 ) amide ( 5 microgram ) . ^^^ In the second experiment , rats were infused with 0 , 10 , or 20 microgram of the GLP 1 receptor antagonist ICV , followed by injection of 0 . 15 M LiCl ( 50 mg / kg ip ) or the same volume of 0 . 15 M NaCl . ^^^ The ability of LiCl treatment to suppress food intake was significantly attenuated in rats that were pretreated with the GLP 1 receptor antagonist . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Finally , the GLP 1 receptor antagonist exendin 3 ( 9 39 ) inhibited the actions of GLP 1 . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
It is well known that the GLP 1 receptor is highly specific for GLP 1 and does not bind other peptides of the glucagon superfamily . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Furthermore , the GLP 1 receptor is expressed in both neurons and glia . ^^^ Because after a penetrating injury a large population of astrocytes become activated and augment their expression of numerous substances , we have used in situ hybridization to determine whether the expression of the GLP 1 receptor increases in response to a penetrating injury . ^^^ We have found that GLP 1 receptor expression increases dramatically along the border of the injury . ^^^ Furthermore , this expression can be colocalized to glial fibrillary acidic protein ( GFAP ) and non GFAP mRNA containing cells , suggesting that at least part of this increase is due to an increase in GLP 1 receptor expression in glial cells . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Thus , regionally distinct GLP 1 receptor populations in the CNS may be involved in satiety or malaise . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
To test this hypothesis , we pretreated rats with a selective and potent GLP 1 receptor antagonist given directly into the third ventricle via an indwelling cannula before administration of peripheral LiCl . ^^^ The GLP 1 receptor antagonist completely blocked the effect of LiCl to reduce food intake , induce pica , and produce a conditioned taste aversion . ^^^ The same dose of GLP 1 receptor antagonist did not reverse the LiCl induced reduction in NaCl intake . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
GLP 1 receptor affinity was highest for imi GLP 1 , followed by alpha me GLP 1 and N me GLP 1 . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The hepatic vagal reception of intraportal GLP 1 is via receptor different from the pancreatic GLP 1 receptor . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
GLP 1 had a potency ( EC ( 50 ) ) of 55 pM for the cloned human GLP 1 receptor . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
This inhibitor also improved glucose tolerance in GLP 1 receptor ( / ) mice , indicating that CD 26 contributes to blood glucose regulation by controlling the activity of GLP 1 as well as additional substrates . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Intracerebroventricular administration of the GLP 1 receptor antagonist exendin ( 9 39 ) ( 10 nmol / rat ) reversed the increases induced by GLP 1 ( 500 pmol / rat ; P < 0 . 01 ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In contrast to previous studies , these findings show that peripheral ( s . c . ) administration of both GLP 1 receptor agonists also induces satiety and weight loss in rats , and suggest the potential usefulness of exendin 4 as a therapeutic tool for the treatment of diabetes and / or obesity . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The GLP 1 receptor agonist exendin 4 showed similar effects , whereas the receptor antagonist exendin ( 9 39 ) amide inhibited the GLP 1 induced increase in insulin receptor binding . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
GLP 1 produced a dose dependent stimulation of 410RIP1 LUC ( EC 50 0 . 43 nmol / l ) , an effect reproduced by the GLP 1 receptor agonist exendin 4 and abolished by the antagonist exendin ( 9 39 ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In contrast , no constitutive activity was observed for GLP 1 receptor , yet responses to GLP 1 indicated that receptor expression had taken place . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Increases in plasma glucagon like peptide 1 ( GLP 1 ) levels and islet GLP 1 receptor mRNA supported increased insulin secretion by HC islets . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The present study examined whether central GLP 1 receptor signaling plays a functional role in LPS induced fever . ^^^ Adult male Sprague Dawley rats were injected i . p . with LPS ( 0 or 100 microg / kg ) , then were infused intracerebroventricularly with GLP 1 receptor antagonist ( 0 or 10 microg ) delivered 2 . 5 h after injection of LPS or vehicle . ^^^ The pyrogenic effect of LPS was amplified in rats that received central infusion of GLP 1 receptor antagonist , although the antagonist by itself did not alter body temperature . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
GLP 1 receptor signaling appears essential for beta cell signal transduction as exemplified by studies of GLP 1R / mice . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
This review highlights recent advances in our understanding of GLP 1 physiology and GLP 1 receptor signaling , and summarizes current pharmaceutical strategies directed at sustained activation of GLP 1 receptor dependent actions for glucoregulation in vivo . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In contrast , coinfusion of glucose and the GLP 1 receptor antagonist exendin ( 9 39 ) into the portal vein at a rate of 0 . 5 pmol / kg . min ( P Ex mice ) reduced glucose clearance to 36 . 1 + / 2 . 6 ml / kg . min and transiently increased glycemia to 9 . 2 + / 0 . 3 mmol / l at 60 min of infusion before it returned to the fasting level ( 5 . 6 + / 0 . 3 mmol / l ) at 3 h . ^^^ Finally , portal vein infusion of glucose in GLP 1 receptor ( / ) mice failed to increase the glucose clearance rate ( 26 . 7 + / 2 . 9 ml / kg . min ) . ^^^ Together , our data show that the GLP 1 receptor is part of the hepatoportal glucose sensor and that basal fasting levels of GLP 1 sufficiently activate the receptor to confer maximum glucose competence to the sensor . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
As with GLP 1 Gly ( 8 ) , the binding affinity of GLP 1 Aha ( 8 ) for the GLP 1 receptor in intact Chinese hamster ovary ( CHO ) cells expressing the human GLP 1 receptor ( CHO / GLP 1R cells ) was reduced ( IC ( 50 ) : GLP 1 , 3 . 7 + / 0 . 2 nM ; GLP 1 Gly ( 8 ) , 41 + / 9 nM ; GLP 1 Aha ( 8 ) , 22 + / 7 nM ) . ^^^ They had poor binding affinity for the GLP 1 receptor , and none of these compounds stimulated the production of intracellular cAMP in CHO / GLP 1R cells or insulin secretion in RIN 1046 38 cells . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
As GLP 1 exhibits a short t ( 12 ) in vivo , the biological consequences of prolonged GLP 1 receptor signaling remains unclear . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Exendin ( 9 39 ) amide , a GLP 1 receptor antagonist , prevented the GLP 1 induced depolarization . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In vitro folding , functional characterization , and disulfide pattern of the extracellular domain of human GLP 1 receptor . ^^^ The N terminal , extracellular domain of the receptor for glucagon like peptide 1 ( GLP 1 receptor ) was expressed at a high level in E . coli and isolated as inclusion bodies . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The effect of LY 315902 and GLP 1 on fasting small bowel motility was dose dependent and treatment with exendin ( 9 39 ) amide , a GLP 1 receptor antagonist , together with LY 315902 and GLP 1 completely antagonised the inhibitory effect of LY 315902 and GLP 1 on fasting small bowel motility . ^^^ The effect of LY 315902 on motor control is mediated through the GLP 1 receptor and seems partly dependent on the L arginine / NO pathway . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
CICR was triggered by the GLP 1 receptor agonist exendin 4 , an effect mimicked by caffeine , Sp cAMPS or forskolin . ^^^ It is concluded that CICR in INS 1 cells results from GLP 1 receptor mediated sensitization of the intracellular Ca2+ release mechanism , a signal transduction pathway independent of PKA , but which requires cAMP GEF II . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
GLP 1 containing nerve fibres and the GLP 1 receptor are found predominantly in hypothalamic midline nuclei . ^^^ In contrast to the widely distributed GLP 1 receptor mRNA , GLP 2 receptor mRNA is exclusively expressed in the compact part of the DMH ( DMHc ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
We report on the effects of GLP 1 and two of its long acting analogs , exendin 4 and exendin 4 WOT , on neuronal proliferation and differentiation , and on the metabolism of two neuronal proteins in the rat pheochromocytoma ( PC 12 ) cell line , which has been shown to express the GLP 1 receptor . ^^^ We observed that GLP 1 and exendin 4 induced neurite outgrowth in a manner similar to nerve growth factor ( NGF ) , which was reversed by coincubation with the selective GLP 1 receptor antagonist exendin ( 9 39 ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The specificity of both antagonists was demonstrated by their selective interaction with glucagon receptor signaling in rat hepatocytes and GLP 1 receptor signaling in Chinese hamster lung ( CHL ) fibroblasts . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Furthermore , the contrasting responses of exendin and GLP 1 in 3T3 adipocytes suggest that the peripheral insulin sensitizing effect of exendin 4 ( in contrast to the insulinotropic effect ) does not involve the GLP 1 receptor pathway . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
No inhibition of influx by the selective GLP 1 receptor antagonist exendin ( 9 39 ) , suggesting that the GLP 1 receptor is not involved in the rapid entry into brain . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
At the end of treatment , basal plasma GLP 1 levels were increased , and pancreatic gene expression for GLP 1 receptor was significantly upregulated . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Further evidence for a GLP 1 receptor in this tissue , different from that of the pancreas , is also illustrated , suggesting a role for an inositolphosphoglycan ( IPG ) as at least one of the possible second messengers of the GLP 1 action in human muscle . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
GLP 1 receptor signaling contributes to anorexigenic effect of centrally administered oxytocin in rats . ^^^ In the first experiment , rats were infused centrally with GLP 1 receptor antagonist or vehicle , followed by an anorexigenic dose of synthetic OT . ^^^ The anorexigenic effect of OT was eliminated in rats pretreated with the GLP 1 receptor antagonist . ^^^ These findings implicate endogenous GLP 1 receptor signaling as an important downstream mediator of anorexia in rats after activation of central OT neural pathways . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
We have investigated the acute effects of preproglucagon derived peptides ( PGDP ) glucagon , glucagon like peptide 1 ( GLP 1 ) , glucagon like peptide 2 ( GLP 2 ) , and exendin 4 ( EX 4 ) , a GLP 1 receptor agonist , on thyrotropin ( TSH ) secretion in the rat . ^^^ Moreover , obtained results suggest that both EX 4 and EX ( 9 39 ) evoked inhibition of TSH secretion in the rat is not dependent on their interaction with GLP 1 receptor only . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The mechanism by which DMSO imparts this amplifying action is unclear but may involve redistribution of intracellular compartments or a direct molecular interaction with a downstream target of the GLP 1 receptor signaling pathway in the beta cell . ^^^ These effects of DMSO on incretin action may provide novel applications with respect to further characterizing GLP 1 receptor signaling , identifying incretin like compounds in screening assays , and as a therapeutic treatment in type 2 diabetes . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Exendin 4 ( 1 39 ) ( Ex 4 ) , isolated from Gila monster venom , is a highly specific GLP 1 receptor agonist that exhibits a prolonged duration of action in vivo . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
GLP 1 reduced recombinant K ( ATP ) channel currents by 54 . 1 + / 6 . 9 % in mammalian cells coexpressing SUR 1 , Kir6 . 2 , and GLP 1 receptor clones . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
We examined whether GLP 1 receptor signaling modifies the cellular susceptibility to apoptosis . ^^^ Conversely , mice with a targeted disruption of the GLP 1 receptor gene exhibited increased beta cell apoptosis after STZ administration . ^^^ These findings demonstrate that GLP 1 receptor signaling directly modifies the susceptibility to apoptotic injury , and provides a new potential mechanism linking GLP 1 receptor activation to preservation or enhancement of beta cell mass in vivo . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Additionally , expression of the GLP 1 receptor in whole pancreas was increased 2 . 3 fold in the fat fed dogs . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Exendin 4 is an agonist of the GLP 1 receptor . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Here , we report that GLP 1 receptor signaling also regulates the activity of beta cell voltage dependent K ( + ) ( K ( 5 ) ) channels , themselves potent glucose dependent regulators of insulin secretion . ^^^ GLP 1 receptor activation with exendin 4 ( 10 ( 8 ) mol / l ) in rat beta cells antagonized K ( 5 ) currents by 43 . 3 + / 6 . 3 % , whereas the GLP 1 receptor antagonist exendin 9 39 had no effect . ^^^ The effect of GLP 1 receptor activation on K ( 5 ) currents could be replicated ( current reduction of 55 . 7 + / 6 . 0 % ) by G protein activation with GMP PNP ( 10 nmol / l ) . ^^^ The cAMP pathway antagonist Rp cAMPS ( 100 micro mol / l ) prevented current inhibition by exendin 4 , implicating cAMP signaling in GLP 1 receptor modulation of beta cell K ( 5 ) currents . ^^^ The present results demonstrate that GLP 1 receptor signaling can antagonize beta cell repolarization by reducing voltage dependent K ( + ) currents , an effect likely to contribute to GLP 1 ' s glucose dependent insulinotropic effect . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
We have recently reported that GLP 1 and several longer acting analogs that bind at the GLP 1 receptor , possess neurotrophic properties , and offer protection against glutamate induced apoptosis and oxidative injury in cultured neuronal cells . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Competition binding studies demonstrated that the N terminal domain of the GLP 1 receptor maintains high affinity for the agonist exendin 4 as well as the antagonists exendin 4 ( 3 39 ) and exendin 4 ( 9 39 ) whereas , in contrast , GLP 1 affinity was greatly reduced . ^^^ These data are consistent with a model for the binding of peptide ligands to the GLP 1 receptor in which the central and C terminal regions of the peptides bind to the N terminus of the receptor , whereas the N terminal residues of peptide agonists interact with the extracellular loops and transmembrane helices . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
These findings demonstrate the benefits of a 3 h infusion of GLP 1 on beta cell function beyond those of an acute insulin secretagogue , and support the development of strategies using continuous or prolonged GLP 1 receptor agonism for treating diabetic patients . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In addition , bilateral CeA administration of 2 . 5 microg of a GLP 1 receptor antagonist before intraperitoneal administration of the toxin lithium chloride resulted in a diminished CTA . ^^^ Together , these data indicate that separate GLP 1 receptor populations mediate the multiple responses to GLP 1 . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Finally , we examined the local role of endogenous GLP 1 by specific GLP 1 receptor blockade . ^^^ LH microinjections of exendin ( 9 39 ) amide , a GLP 1 receptor antagonist , at 1 or 2 . 5 microg did not alter feeding behavior in 24 h fasted rats . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The delay in crop emptying induced by GLP 1 ( 15 pmol ) was partly attenuated by co administration with exendin ( 5 39 ) ( 600 pmol ) , a GLP 1 receptor antagonist , although exendin ( 5 39 ) alone did not affect crop emptying . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
AIMS / HYPOTHESIS : This study examined the biological effects of the GIP receptor antagonist , ( Pro 3 ) GIP and the GLP 1 receptor antagonist , exendin ( 9 39 ) amide . ^^^ In GLP 1 receptor transfected fibroblasts , exendin ( 9 39 ) amide inhibited GLP 1 stimulated cyclic AMP production with maximal inhibition of 60+ / 0 . 7 % at 10 ( 6 ) mol / l , whereas ( Pro ( 3 ) ) GIP had no effect . ( Pro ( 3 ) ) GIP specifically inhibited GIP stimulated insulin release ( 86 % ; p < 0 . 001 ) from clonal BRIN BD 11 cells , but had no effect on GLP 1 stimulated insulin release . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
We have shown that activation of the GLP 1 receptor inhibits H ( 2 ) O ( 2 ) induced apoptosis in a cultured mouse insulinoma cell line , termed MIN 6 . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The natural GLP 1 receptor agonist exendin 4 , found in the saliva of the Gila monster , has a longer biological half life after subcutaneous injection than GLP 1 , and inhibition of DPP 4 using , for example , pyrrolidine derivatives provides elevated concentrations of intact , biologically active GIP and GLP 1 endogenously released from the gut . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
GLP 1 receptor agonists are growth and differentiation factors for pancreatic islet beta cells . ^^^ This leads us to propose that GLP 1 and GLP 1 receptor agonists , in the context of long term treatment of type 2 diabetes , will have broader biological action on the endocrine pancreas than was earlier anticipated . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The GLP 1 / 2 containing neural pathways have been suggested to play a role in taste aversion and nausea because LiCl activates these neurons , and LiCl induced suppression of food intake can be blocked by the GLP 1 receptor antagonist exendin 9 . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Substitution of distinct segments of the glucagon receptor core domain with the corresponding segments of the GLP 1 receptor rescued the affinity and potency of specific glucagon analogs . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
It was recently reported that GLP 1 and exendin 4 , a naturally occurring , more stable analogue of GLP 1 that binds at the GLP 1 receptor , possess neurotrophic properties and can protect neurons against glutamate induced apoptosis . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Exendin 4 , a GLP 1 receptor agonist , interacts with proteins and their products of digestion to suppress food intake in rats . ^^^ The GLP 1 receptor agonist , Exendin 4 ( Ex 4 ) ( 0 . 5 micro g / rat ) , was given intraperitoneally to male Wistar rats , and food intake was measured when Ex 4 was given alone or with preloads of intact whey and casein proteins , their hydrolysates and amino acid mixtures ( 0 . 5 g 10 4 mL ( 1 ) 10 rat ( 1 ) ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
This is due , at least in part , to a heightened response of the mutant GLP 1 receptor to multiple sources of the somatic ligand LAG 2 , including the proximal somatic gonad . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
To develop non beta cells that exhibit physiologically regulated insulin secretion , we coexpressed the GLP 1 receptor and human insulin in primary rat pituitary cells using adenovirus mediated gene transfer . ^^^ Normal pituitary cells do not express the GLP 1 receptor as shown by the absence of GLP 1 receptor mRNA and the inability of GLP 1 to stimulate pituitary hormone secretion . ^^^ Following transduction with an adenovirus carrying the GLP 1 receptor cDNA , the pituitary cells expressed functional GLP 1 receptors as reflected by the ability of GLP 1 to stimulate secretion of pituitary hormones . ^^^ When both the GLP 1 receptor and human insulin were introduced , GLP 1 stimulated cosecretion of human insulin and endogenous pituitary hormones . ^^^ After transplantation of pituitary cells coexpressing human insulin and GLP 1 receptor into mice , enteral glucose stimulated insulin secretion . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Successful strategies to overcome this difficulty are the use of DPPIV resistant GLP 1 receptor agonists , such as NN 2211 or exendin 4 , and the use of inhibitors of DPPIV , such as NVPDPP 728 and P32 / 98 . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Receptor binding studies demonstrated that the affinity of ZP10A for the human GLP 1 receptor was 4 fold greater than the affinity of GLP 1 ( 7 36 ) amide . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
CONCLUSION / INTERPRETATION : This study identifies type 8 AC in insulin secreting cells as one of the potential molecular targets for synergism between GLP 1 receptor mediated and glucose mediated signalling . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
AC 2993 ( Exendin 4 ) is a naturally occurring peptide isolated from the lizard Heloderma , and it acts as a high affinity agonist at the GLP 1 receptor . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In the adult hermaphrodite , reduction of SEC 23 function by RNA mediated interference caused a rapid onset of sterility , with defects in oogenesis including early maturation of the germline nuclei , probably a result of the observed loss of the GLP 1 receptor from the membrane surfaces adjacent to the developing germline nuclei . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The mechanism and signaling pathway regulating these currents in rat beta cells were investigated using the GLP 1 receptor agonist exendin 4 . ^^^ Therefore , antagonism of beta cell Kv currents by GLP 1 receptor activation requires both cAMP / PKA and PI 3 kinase / PKCzeta signaling via trans activation of the EGF receptor . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Glucagon like peptide ( GLP ) 1 binds to GLP 1 receptor ( with a Kd of 0 . 2 nM ) signals through Galpha ( s ) to activate adenylate cyclase , which results in an increase of intracellular cAMP ( EC ( 50 ) of 0 . 3 nM ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Despite evidence that the GLP 1 receptor is present and active in neurons , little is known of the roles of GLP 1 in neuronal physiology . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Glucagon like peptide 1 ( GLP 1 ) and GLP 1 receptor agonists increase the beta cell mass in rodent models of type 2 diabetes and enhance the proliferation rate of beta cells in vitro , while the long term effect in vivo in non diabetic animals is unknown . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Gene expression of the GLP 1 receptor was clearly detected by both RT PCR and Northern blot analysis . ^^^ However , semi quantitative RT PCR revealed that the ratio of the gene expression level of the GIP receptor to that of the GLP 1 receptor was less than 1 : 250 , indicating that receptor gene expression of GIP is practically negligible in the ganglion . ^^^ Additionally , an equal level of GLP 1 receptor gene expressions between left and right side ganglia was evidenced by semi quantitative RT PCR , implying possible extrahepatic occurrence of vagal GLP 1 reception in addition to the reception through the hepatic vagus ( originating from the left side ganglion ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
This analogue , ( Lys ( 9 ) ) GLP 1 , exhibited a preserved GLP 1 receptor affinity , but the usual stimulatory effects of GLP 1 were completely eliminated , a trait duplicated by the other established GLP 1 antagonists , exendin ( 9 39 ) and GLP 1 ( 9 36 ) amide . ^^^ We investigated the in vivo antagonistic actions of ( Lys ( 9 ) ) GLP 1 in comparison with GLP 1 ( 9 36 ) amide and exendin ( 9 39 ) and revealed that this novel analogue may serve as a functional antagonist of the GLP 1 receptor . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The primary ligand binding interaction at the GLP 1 receptor is via the putative helix of the peptide agonists . ^^^ The N terminal domain of the GLP 1 receptor binds the putative helical region of the peptide agonists , GLP 1 and exendin 4 . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Met 204 and Tyr 205 are together important for binding GLP 1 receptor agonists but not their N terminally truncated analogues . ^^^ A mutagenesis study to systematically analyse residues spanning the first extracellular loop of the GLP 1 receptor identified a double mutant , Met 204 / Tyr 205 Ala / Ala , which displayed : markedly reduced affinity for the natural agonist GLP 1 ; slightly reduced affinity for its analogue exendin 4 ; and unaltered affinity for several N terminally truncated analogues of GLP 1 and exendin 4 . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The actions of glucagon were unaffected by the GLP 1 receptor antagonist exendin ( 9 39 ) but abolished by des His 1 [ Glu 9 ] glucagon amide , a specific blocker of the glucagon receptor . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
To prolong GLP 1 bioactivity , DPPIV resistant GLP 1 analogues , DPPIV inhibitors and exenatide , a long acting synthetic GLP 1 receptor agonist derived from the Gila monster hormone exendin 4 , have been developed . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
These effects are thought to be mediated by the GLP 1 receptor . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Furthermore , the GLP 1 receptor agonist , Exenatide , dose dependently enhanced phosphorylation of S6K1 at an intermediate glucose concentration ( 8 mmol / l ) in a rapamycin sensitive manner . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The relaxant effect from GLP 1 was completely inhibited by the specific GLP 1 receptor antagonist , exendin ( 9 39 ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The augmented insulin response to GRP by val pyr was prevented by the GLP 1 receptor antagonist , exendin ( 3 ) ( 9 39 ) , raising the possibility that GRP effects may occur secondary to stimulation of GLP 1 secretion . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
This protection was abolished in the in vitro hearts by the GLP 1 receptor antagonist exendin ( 9 39 ) , the cAMP inhibitor Rp cAMP , the PI3kinase inhibitor LY 294002 , and the p42 / 44 mitogen activated protein kinase inhibitor UO 126 . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Activity of secreted GLP 1 Gly 8 was assayed using Chinese hamster lung fibroblasts ( CHL ) cells that expressed cloned GLP 1 receptor and that were transfected with CRE Luc . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The GLP 1 HSA bioconjugates were analyzed in vitro to assess the stabilizing effect of bioconjugation in the presence of DPP 4 as well as GLP 1 receptor binding and activation . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
GLP 1 receptor agonists depolarized hypocretin neurons and increased their spike frequency ; the antagonist exendin ( 9 39 ) blocked this depolarization . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Analysis of mice with inactivation of the GLP 1 receptor gene has provided evidence that absence of GLP 1 action in the mouse , despite this hormone potent physiological effects when administered in vivo , only leads to mild abnormalities in glucose homeostasis without any change in body weight . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The GLP 1 receptor is a Class B heptahelical G protein coupled receptor that stimulates cAMP production in pancreatic beta cells . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
From these results we conclude that while GLP 1 does not seem to induce beta cell lipolysis acutely in mouse islets , the peptide affects beta cell fat metabolism after long term adaptation to GLP 1 receptor stimulation . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Thus , GLP 1 receptor agonists are being intensively developed for the treatment of human diabetes and are likely to become available to clinical use in the near future . ^^^ Evidence suggesting a role for endogenous GLP 1 and GLP 1 receptor during beta cell development will be reviewed . ^^^ Finally , the therapeutic potential for intervention with GLP 1 receptor agonists during the neonatal period will be discussed . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
For more long term metabolic control , incretin mimetics ( agonists at the GLP 1 receptor ) with more favourable pharmacokinetic profiles should be used . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
GLP 1 receptor agonists and DPP 4 inhibitors in the treatment of type 2 diabetes . ^^^ One is to use GLP 1 receptor agonists that have a prolonged half life due to reduced degradation by DPP 4 . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
New therapeutic strategies and drug candidates for neurodegenerative diseases : p 53 and TNF alpha inhibitors , and GLP 1 receptor agonists . ^^^ Such targets include TNF alpha , p 53 , and GLP 1 receptor . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Human studies employing the specific GLP 1 receptor antagonist exendin ( 9 39 ) show that endogenously released GLP 1 likewise controls fasting plasma glucagon , stimulates insulin , and influences all the motoric mechanisms known to control gastric emptying . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
One strategy is the use of DPP 4 resistant GLP 1 receptor agonists ( exenatide and liraglutide ) and another strategy is to inhibit DPP 4 activity ( LAF 237 ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Exendin ( 9 39 ) , described as a GLP 1 receptor antagonist , inhibited contraction due to glicentin or GLP 1 . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The endogenous beta cell GLP 1 receptor is coupled to adenylyl cyclase , cell depolarization , activation of voltage dependent Ca2+ channels ( VDCC ) and extracellular Ca2+ influx ( Lu et al . , 1993 b ) . ^^^ In contrast , the signaling pathways of the GLP 1 receptor in alpha cells are poorly understood . ^^^ To determine the signaling mechanisms of the alpha cell GLP 1 receptor , we established a stable pancreatic islet alpha cell line expressing the recombinant rat GLP 1 receptor ( INR 1 SF2 ) , using INRl G 9 cells . ^^^ These INRl G 9 cells do not express endogenous GLP 1 receptor . ^^^ This study establishes that a single GLP 1 receptor species can mediate the effects of GLP 1 through multiple signaling pathways , including the adenylyl cyclase system and intracellular Ca2+ release , in an alpha cell type . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Hyperglycemia after protein ingestion concurrent with injection of a GLP 1 receptor agonist in rats : a possible role for dietary peptides . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Pretreatment with exendin ( 9 39 ) , a GLP 1 receptor antagonist , attenuated the leptin induced increase in CRH content of the hypothalamus . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Pre treatment with exendin 4 ( 10 ( 7 ) mol / l ) , a long acting GLP 1 receptor agonist , partially protected the cells against cytokine induced toxicity ( p < 0 . 01 ) in association with a reduction in cytokine induced inhibition of PKB phosphorylation ( p < 0 . 05 ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Male C57BL / 6 mice were injected ( ip ) with exendin 4 ( 1 39 ) ( Ex 4 , a GLP 1 receptor agonist ) and / or PYY ( 3 36NH2 ) ( 0 . 03 3 microg ) , and FI was determined for up to 24 h . ^^^ Similarly , exendin 4 ( 9 39 ) ( a GLP 1 receptor antagonist ) partially abolished Ex 4 induced anorexia ( P < 0 . 05 ) , but did not affect the satiation produced by PYY ( 3 36NH2 ) . ^^^ Thus , Ex 4 and PYY ( 3 36NH2 ) suppress FI via independent mechanisms involving a GLP 1 receptor dependent , sensory afferent pathway ( Ex 4 ) and a Y 2 receptor mediated pathway ( PYY ( 3 36NH2 ) ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The anti apoptotic effect of liraglutide was mediated by the GLP 1 receptor as the specific GLP 1 receptor antagonist , exendin ( 9 39 ) , blocked the effects . ^^^ In conclusion , GLP 1 receptor activation has anti apoptotic effect on both cytokine , and free fatty acid induced apoptosis in primary islet cells , thus suggesting that the long acting GLP 1 analogue , liraglutide , may be useful for retaining beta cell mass in both type 1 and type 2 diabetic patients . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In this work we analysed the substitution of Cys 438 by alanine in the glucagon like peptide 1 ( GLP 1 ) receptor ( GLPR ) , which led to a threefold decrease in cAMP production , although endocytosis and cellular redistribution of GLP 1 receptor agonist induced processes were unaffected . ^^^ Thus , cysteine 438 in the cytoplasmic tail of the GLP 1 receptor would regulate its interaction with G proteins and the stimulation of adenylyl cyclase . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
This study has employed the GLP 1 receptor antagonist , exendin 4 ( 9 39 ) amide ( Ex ( 9 39 ) ) to evaluate the role of endogenous GLP 1 in genetic obesity related diabetes and related metabolic abnormalities using ob / ob and normal mice . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In rat insulin secreting INS 1 cells or mouse beta cells loaded with caged Ca2+ ( NP EGTA ) , a GLP 1 receptor agonist ( exendin 4 ) is demonstrated to sensitize intracellular Ca2+ release channels to stimulatory effects of cytosolic Ca2+ , thereby allowing CICR to be generated by the uncaging of Ca2+ ( UV flash photolysis ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Expression and purification of exendin 4 , a GLP 1 receptor agonist , in Escherichia coli . ^^^ Exendin 4 is a potent and long acting agonist of GLP 1 receptor . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Our findings indicate that the neighbouring trans membrane domain of the carboxyl terminal tail of the GLP 1 receptor contains sequence elements that regulate agonist dependent internalisation and transmembrane signalling . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
However , prolonged GLP 1 treatment resulted in GLP 1 receptor desensitization regardless of DPP 4 status . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
We showed previously that the C terminally truncated exendin peptide exendin ( 1 30 ) has a reduced affinity for the GLP 1 receptor and a diminished ability to increase intracellular cAMP in insulinoma cells . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The GLP 1 receptor was present at all five stages of the culture . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The GLP 1 receptor is expressed in a variety of other tissues important for carbohydrate metabolism , including pancreatic alpha cells , hypothalamus and brainstem , and proximal intestinal tract . ^^^ Thus , because of its multiple actions , GLP 1 is an attractive therapeutic target for the treatment of type 2 diabetes , and major interest has resulted in the development of a variety of GLP 1 receptor agonists for this purpose . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
These results are consistent with exendin 4 having cardiovascular effects through GLP 1 receptor dependent and independent mechanisms , some of which involve sympathoadrenal activation . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The reduction of post prandial circulating active GLP 1 in Type 2 diabetic subjects , as a consequence of chronic hyperglycemia , could contribute to the reduction of early post prandial insulin secretion ; in fact , the administration of GLP 1 receptor antagonists to healthy volunteers elicits both an impairment of meal induced insulin secretion and an increase of post prandial glycemia similar to that observed in Type 2 diabetes . ^^^ There are now several compounds in various stages of pre clinical or clinical development for the treatment of Type 2 diabetes that utilize the GLP 1 signaling pathway ; these include GLP 1 receptor agonists with extended half lives , and inhibitors of DPP 4 that increase circulating levels of endogenous , intact and bioactive GLP 1 . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
In mice undergoing a hyperglycemic hyperinsulinemic clamp , icv administration of the specific GLP 1 receptor antagonist exendin 9 39 ( Ex 9 ) increased muscle glucose utilization and glycogen content . ^^^ Conversely , icv infusion of the GLP 1 receptor agonist exendin 4 ( Ex 4 ) reduced insulin stimulated muscle glucose utilization . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
AIMS : To assess the effects of endogenous GLP 1 on endocrine pancreatic secretion and antro pyloro duodenal motility by utilising the GLP 1 receptor antagonist exendin ( 9 39 ) amide ( ex ( 9 39 ) NH 2 ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The GLP 1 receptor agonist , exendin 4 , has a longer duration of action , and has recently been approved as a new agent for the treatment of type 2 diabetes mellitus . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Targeted mutations were incorporated into the optimal dual receptor binding peptide to identify a peptide with the highly novel property of functioning as both a GLP 1 receptor agonist and a glucagon receptor antagonist . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
This article summarizes current concepts of incretin action and highlights the potential therapeutic utility of GLP 1 receptor agonists and dipeptidyl peptidase 4 ( DPP 4 ) inhibitors for the treatment of type 2 diabetes . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
GLP 1 acts via a G protein coupled receptor , and PI 3 Kgamma is known to be activated by G ( betagamma . ) Therefore , the role of PI 3 Kgamma in the chronic effects of GLP 1 on the beta cell was investigated using PI 3 Kgamma knockout ( KO ) mice treated with the GLP 1 receptor agonist , exendin 4 ( Ex 4 ; 1 nmol / kg sc every 24 h for 14 d ) . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The GLP 1 receptor is widely distributed and has been identified in the endocrine pancreas , intestinal tract , brain , lung , kidney , and heart . ^^^ Here we report the expression of the GLP 1 receptor and proglucagon in the skin of newborn mice located predominantly in the hair follicles , as well as in cultures of skin derived cells that also express nestin , a marker of cultured cells that have dedifferentiated by epithelial to mesenchymal transition . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
GLP 1 binding and GLP 1 receptor mRNA expression were observed in both astrocytes and microglia . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Exendin 4 , a GLP 1 receptor agonist first isolated from the venom of the Gila monster Heloderma suspectum , is a clinically valuable , long acting incretin and the skins of several species of frogs synthesize potent insulin releasing peptides with therapeutic potential . . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
GLP 1 receptor activation also augments insulin biosynthesis , restores beta cell sensitivity to glucose , increases beta cell proliferation , and reduces apoptosis , leading to expansion of the beta cell mass . ^^^ A GLP 1 receptor agonist , exendin 4 , has recently been approved for the treatment of type 2 diabetes in the US . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
The glucagon like peptide 1 receptor binding site for the N terminus of GLP 1 requires polarity at Asp 198 rather than negative charge . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
We mapped the positions of actively dividing germline nuclei in over 600 fixed gonad preparations including the wild type and a gain of function ligand responsive GLP 1 receptor mutant with an extended mitotic zone . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
Administration of a GLP 1 receptor antagonist , GLP 1 ( 9 39 ) , resulted in decreased recovery of beta cells after STZ and worse glucose tolerance . ^^^
Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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Interacting proteins: P43220 and P01275	Pubmed	SVM Score :0.0
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