GPR119 agonists mediate GLP-1 secretion from mouse enteroendocrine cells through glucose-independent pathways.

Lan, H., Lin, H.V., Wang, C.F., Wright, M.J., Xu, S., Kang, L., Juhl, K., Hedrick, J.A., Kowalski, T.J.
Journal   Br J Pharmacol.
Species  
Analytes Measured   GLP-1 , Insulin
Matrix Tested   Cell culture supernatants
Year   2011
Volume  
Page Numbers  
Application   Metabolic
Abstract
Background and purpose:  GPR119 mediates insulin secretion from pancreatic β cells and 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 requires the presence of glucose. This study is 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 in the presence and absence of glucose was analyzed in the intestinal L cell line GLUTag, in primary intestinal cell culture, and in vivo. Insulin secretion from Min6 cells, a pancreatic β cell line, was analyzed 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 culture, GPR119 agonists stimulated GLP-1 secretion under glucose-free condition. Moreover, a GPR119 agonist increased plasma GLP-1 in mice without a glucose load. In contrast, GPR119-mediated insulin secretion in Min6 cells required the presence of glucose. 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:  In contrast to that in pancreatic β cells, GPR119-mediated GLP-1 secretion from intestinal L cells is glucose-independent in vitro and in vivo, likely due to a higher basal calcium tone in the L cells.

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