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

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Juris J Meier, Michael A Nauck, Andrea Pott, Kai Heinze, Oliver Goetze, Kerem Bulut, Wolfgang E Schmidt, Baptist Gallwitz, Jens Juul Holst

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.

Original languageEnglish
JournalGastroenterology
Volume130
Issue number1
Pages (from-to)44-54
Number of pages11
ISSN0016-5085
DOIs
Publication statusPublished - Jan 2006

    Research areas

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

ID: 132053274