A human cellular model for studying the regulation of glucagon-like peptide-1 secretion

GLP-1 (glucagon-like peptide-1) is a potent insulin secretagogue released f rom L cells in the intestine. The regulation of GLP-1 secretion has been de scribed both in vivo and in vitro in several animal species, but data from human cellular models are lacking. For this purpose, factors and cell-signa ling pathways regulating GLP-1 secretion were investigated in the NCI-H716 human intestinal cell line. After differentiation, these cells homogeneousl y 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 m eat hydrolysate, stimulated GLP-1 secretion in a dose-dependent manner, as did the cholinergic agonist carbachol and the neuromediator gastrin-releasi ng 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 NCT-H716 cells. However, neither PKA activators nor meat hydrolysate increased proglucagon mRNA lev els. These findings indicate that the NCI-H716 cell line constitutes a uniq ue model to study the cellular mechanism of GLP-1 secretion in humans and s uggest potential interspecies divergence in the regulation of proglucagon g ene expression in enteroendocrine cells.