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

TY - JOUR

T1 - Glucagon-like peptide 2 stimulates glucagon secretion, enhances lipid absorption, and inhibits gastric acid secretion in humans

AU - Meier, Juris J

AU - Nauck, Michael A

AU - Pott, Andrea

AU - Heinze, Kai

AU - Goetze, Oliver

AU - Bulut, Kerem

AU - Schmidt, Wolfgang E

AU - Gallwitz, Baptist

AU - Holst, Jens Juul

PY - 2006/1

Y1 - 2006/1

N2 - 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.

AB - 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.

KW - Adult

KW - Fasting

KW - Fatty Acids

KW - Gastric Acid

KW - Gastric Emptying

KW - Glucagon

KW - Glucagon-Like Peptide 2

KW - Glucagon-Like Peptides

KW - Humans

KW - Hypoglycemic Agents

KW - Infusions, Intravenous

KW - Insulin

KW - Lipid Metabolism

KW - Male

KW - Placebos

KW - Postprandial Period

U2 - 10.1053/j.gastro.2005.10.004

DO - 10.1053/j.gastro.2005.10.004

M3 - Journal article

C2 - 16401467

SN - 0016-5085

VL - 130

SP - 44

EP - 54

JO - Gastroenterology

JF - Gastroenterology

IS - 1

ER -