Document Detail

Agonists at GPR119 mediate secretion of GLP-1 from mouse enteroendocrine cells through glucose-independent pathways.
MedLine Citation:
PMID:  22029751     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article    
Journal Detail:
Title:  British journal of pharmacology     Volume:  165     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-26     Completed Date:  2012-07-27     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  2799-807     Citation Subset:  IM    
Copyright Information:
© 2011 Merck Sharp & Dohme Corp. British Journal of Pharmacology © 2011 The British Pharmacological Society.
Diabetes and Endocrinology, Merck Research Laboratories, Rahway, NJ, USA Biologics, Merck Research Laboratories, Rahway, NJ, USA.
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MeSH Terms
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
Mice, Inbred C57BL
Oleic Acids / pharmacology
Receptors, G-Protein-Coupled / agonists*
Reg. No./Substance:
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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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