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 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.
Reimer
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Nestlé Research Center, P.O. Box 44, Vers-Chez-Les-Blanc, 1000 Lausanne 26, Switzerland.
Darimont
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Gremlich
S
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Nicolas-Métral
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V
Rüegg
U T
UT
Macé
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K
D000818:Animals; D002460:Cell Line; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D006801:Humans; D007422:Intestines / Q000502:physiology*; D019301:Oleic Acid / Q000494:pharmacology; D019308:Palmitic Acid / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism*; D011492:Protein Hydrolysates / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism*
D010446:Peptide Fragments; D011492:Protein Hydrolysates; D011498:Protein Precursors; D019301:Oleic Acid; D019308:Palmitic Acid; D052216:Glucagon-Like Peptide 1; D005934:Glucagon