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A Human Cellular Model for Studying the Regulation of Glucagon-Like Peptide-1 Secretion

Nestlé Research Center (R.A.R., C.D., S.G., K.M.), P.O. Box 44, Vers-Chez-Les-Blanc, 1000 Lausanne 26, Switzerland; and Pharmacology Group (V.N.-M., U.T.R.), School of Pharmacy, University of Lausanne, 1015 Lausanne, Switzerland

Address all correspondence and requests for reprints to: Dr. Katherine Macé, Nestlé Research Center, P.O. Box 44, Vers-Chez-Les-Blanc, 1000 Lausanne 26, Switzerland. E-mail: catherine.mace{at}rdls.nestle.com

GLP-1 (glucagon-like peptide-1) is a potent insulin secretagogue released from L cells in the intestine. The regulation of GLP-1 secretion has been described both in vivo and in vitro in several animal species, but data from human cellular models are lacking. For this purpose, factors and cell-signaling pathways regulating GLP-1 secretion were investigated in the NCI-H716 human intestinal cell line. After differentiation, these cells homogeneously produced 16.8 pmol GLP-1/mg protein with a basal release of 4.2% during a 2-h incubation period. Nutrients, such as palmitic acid, oleic acid, and meat hydrolysate, stimulated GLP-1 secretion in a dose-dependent manner, as did the cholinergic agonist carbachol and the neuromediator gastrin-releasing peptide. Along with stimulating GLP-1 release, gastrin-releasing peptide, like ionomycin, increased intracellular calcium levels. Activators of PKA and PKC were able to increase GLP-1 secretion in NCI-H716 cells. However, neither PKA activators nor meat hydrolysate increased proglucagon mRNA levels. These findings indicate that the NCI-H716 cell line constitutes a unique model to study the cellular mechanism of GLP-1 secretion in humans and suggest potential interspecies divergence in the regulation of proglucagon gene expression in enteroendocrine cells.

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