| Agonists at GPR119 mediate secretion of GLP-1 from mouse enteroendocrine cells through glucose-independent pathways. | |
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MedLine Citation:
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PMID: 22029751 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE: The G protein-coupled receptor 119 (GPR119) mediates insulin secretion from pancreatic β cells and glucagon-like peptide 1 (GLP-1) release from intestinal L cells. While GPR119-mediated insulin secretion is glucose dependent, it is not clear whether or not GPR119-mediated GLP-1 secretion similarly requires glucose. This study was designed to address the glucose-dependence of GPR119-mediated GLP-1 secretion, and to explore the cellular mechanisms of hormone secretion in L cells versus those in β cells. EXPERIMENTAL APPROACH: GLP-1 secretion in response to GPR119 agonists and ion channel modulators, with and without glucose, was analysed in the intestinal L cell line GLUTag, in primary intestinal cell cultures and in vivo. Insulin secretion from Min6 cells, a pancreatic β cell line, was analysed for comparison. KEY RESULTS: In GLUTag cells, GPR119 agonists stimulated GLP-1 secretion both in the presence and in the absence of glucose. In primary mouse colon cultures, GPR119 agonists stimulated GLP-1 secretion under glucose-free conditions. Moreover, a GPR119 agonist increased plasma GLP-1 in mice without a glucose load. However, in Min6 cells, GPR119-mediated insulin secretion was glucose-dependent. Among the pharmacological agents tested in this study, nitrendipine, an L-type voltage-dependent calcium channel blocker, dose-dependently reduced GLP-1 secretion from GLUTag cells, but had no effect in Min6 cells in the absence of glucose. CONCLUSIONS AND IMPLICATIONS: Unlike that in pancreatic β cells, GPR119-mediated GLP-1 secretion from intestinal L cells was glucose-independent in vitro and in vivo, probably because of a higher basal calcium tone in the L cells. |
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Authors:
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H Lan; H V Lin; C F Wang; M J Wright; S Xu; L Kang; K Juhl; J A Hedrick; T J Kowalski |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: British journal of pharmacology Volume: 165 ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-03-26 Completed Date: 2012-07-27 Revised Date: 2013-05-23 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 2799-807 Citation Subset: IM |
Copyright Information:
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© 2011 Merck Sharp & Dohme Corp. British Journal of Pharmacology © 2011 The British Pharmacological Society. |
Affiliation:
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Diabetes and Endocrinology, Merck Research Laboratories, Rahway, NJ, USA Biologics, Merck Research Laboratories, Rahway, NJ, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcium / metabolism Cell Line Colon / cytology Enteroendocrine Cells / drug effects*, secretion Forskolin / pharmacology Glucagon-Like Peptide 1 / secretion* Glucose / pharmacology Insulin-Secreting Cells / drug effects*, secretion Male Mice Mice, Inbred C57BL Oleic Acids / pharmacology Receptors, G-Protein-Coupled / agonists* |
| Chemical | |
Reg. No./Substance:
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0/Gpr119 protein, mouse; 0/Oleic Acids; 0/Receptors, G-Protein-Coupled; 0/oleoylethanolamide; 50-99-7/Glucose; 66428-89-5/Forskolin; 7440-70-2/Calcium; 89750-14-1/Glucagon-Like Peptide 1 |
| Comments/Corrections | |
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