| http://purl.uniprot.org/citations/15561912 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15561912 | http://www.w3.org/2000/01/rdf-schema#comment | "Glucagon-like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion and inhibits food intake, gastric emptying, and glucagon secretion, actions that promote reduction of fasting and postprandial glycemia in subjects with type 2 diabetes. 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. PMA (4-phorbol 12-myristate 13-acetate) but not glucagon, glucose-dependent insulinotropic polypeptide (GIP), or epinephrine produced heterologous desensitization in vitro. MT-Ex-4 transgenic mice exhibited a reduced glycemic response to oral but not intraperitoneal glucose challenge following acute Ex-4 administration. In contrast, no differences in glycemic excursion or plasma insulin were observed after 1 week of twice-daily Ex-4 administration to wild-type versus MT-Ex-4 mice. 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. However, repeated Ex-4 administration significantly reduced food intake in MT-Ex-4 but not in wild-type mice. These findings illustrate that although Ex-4 is more potent than native GLP-1 in producing GLP-1 receptor desensitization in vitro, chronic exposure to Ex-4 in normal or transgenic mice is not associated with significant downregulation of GLP-1 receptor-dependent responses coupled to glucose homeostasis in vivo."xsd:string |
| http://purl.uniprot.org/citations/15561912 | http://purl.org/dc/terms/identifier | "doi:10.2337/diabetes.53.suppl_3.s205"xsd:string |
| http://purl.uniprot.org/citations/15561912 | http://purl.uniprot.org/core/author | "Kim J.G."xsd:string |
| http://purl.uniprot.org/citations/15561912 | http://purl.uniprot.org/core/author | "Drucker D.J."xsd:string |
| http://purl.uniprot.org/citations/15561912 | http://purl.uniprot.org/core/author | "Baggio L.L."xsd:string |
| http://purl.uniprot.org/citations/15561912 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
| http://purl.uniprot.org/citations/15561912 | http://purl.uniprot.org/core/name | "Diabetes 53 Suppl"xsd:string |
| http://purl.uniprot.org/citations/15561912 | http://purl.uniprot.org/core/pages | "S205-14"xsd:string |
| http://purl.uniprot.org/citations/15561912 | http://purl.uniprot.org/core/title | "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."xsd:string |
| http://purl.uniprot.org/citations/15561912 | http://purl.uniprot.org/core/volume | "3"xsd:string |
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