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

Endocrinology. 2001 Oct;142(10):4522-8. doi: 10.1210/endo.142.10.8415.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Diet
  • Dose-Response Relationship, Drug
  • Glucagon / metabolism*
  • Glucagon-Like Peptide 1
  • Humans
  • Intestines / physiology*
  • Oleic Acid / pharmacology
  • Palmitic Acid / pharmacology
  • Peptide Fragments / metabolism*
  • Protein Hydrolysates / pharmacology
  • Protein Precursors / metabolism*


  • Peptide Fragments
  • Protein Hydrolysates
  • Protein Precursors
  • Oleic Acid
  • Palmitic Acid
  • Glucagon-Like Peptide 1
  • Glucagon