Glucagon-like peptide 2 stimulates glucagon secretion, enhances lipid absorption, and inhibits gastric acid secretion in humans

Gastroenterology. 2006 Jan;130(1):44-54. doi: 10.1053/j.gastro.2005.10.004.


Background & aims: The gut-derived peptide glucagon-like peptide 2 (GLP-2) has been suggested as a potential drug candidate for the treatment of various intestinal diseases. However, the acute effects of GLP-2 on gastric functions as well as on glucose and lipid homeostasis in humans are less well characterized.

Methods: Fifteen healthy male volunteers were studied with the intravenous infusion of GLP-2 or placebo over 120 minutes in the fasting state, and pentagastrin-stimulated gastric acid output was assessed. Another 15 healthy male volunteers were studied with a 390 minutes infusion of GLP-2 or placebo during the ingestion of a solid test meal. Gastric emptying was determined using a 13C-sodium-octanote breath test. Plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP-2, free fatty acids, free glycerol, and triglycerides were determined.

Results: GLP-2 administration led to a marked increase in glucagon concentrations both in the fasting state and during the meal study (P < .001). Postprandial plasma concentrations of triglycerides and free fatty acids were significantly higher during GLP-2 infusion compared with placebo (P < .01), while glycerol concentrations were similar (P = .07). GLP-2 administration caused an approximately 15% reduction in pentagastrin-stimulated gastric acid and chloride secretion (P < .01), whereas gastric emptying was not affected (P = .99).

Conclusions: GLP-2 reduces gastric acid secretion but does not seem to have an influence on gastric emptying. The stimulation of glucagon secretion by GLP-2 may counteract the glucagonostatic effect of GLP-1. Changes in postprandial lipid excursions seem to reflect enhanced intestinal nutrient absorption during GLP-2 administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Fasting
  • Fatty Acids / metabolism
  • Gastric Acid / metabolism*
  • Gastric Emptying / physiology
  • Glucagon / metabolism*
  • Glucagon-Like Peptide 2
  • Glucagon-Like Peptides / physiology*
  • Humans
  • Hypoglycemic Agents / blood
  • Infusions, Intravenous
  • Insulin / blood
  • Lipid Metabolism*
  • Male
  • Placebos
  • Postprandial Period


  • Fatty Acids
  • Glucagon-Like Peptide 2
  • Hypoglycemic Agents
  • Insulin
  • Placebos
  • Glucagon-Like Peptides
  • Glucagon