Glucagon-like peptide 2 stimulates glucagon secretion, enhances lipid absorption, and inhibits gastric acid secretion in humans.
OBJECTIVE
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.
Meier
Juris J
JJ
Department of Medicine I, St. Josef-Hospital, Ruhr-University, Bochum, Germany. jmeier@mednet.ucla.edu
Nauck
Michael A
MA
Pott
Andrea
A
Heinze
Kai
K
Goetze
Oliver
O
Bulut
Kerem
K
Schmidt
Wolfgang E
WE
Gallwitz
Baptist
B
Holst
Jens J
JJ
D000328:Adult; D005215:Fasting; D005227:Fatty Acids / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism*; D005746:Gastric Emptying / Q000502:physiology; D005934:Glucagon / Q000378:metabolism*; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides / Q000502:physiology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism; D008297:Male; D010919:Placebos; D019518:Postprandial Period
D005227:Fatty Acids; D053767:Glucagon-Like Peptide 2; D007004:Hypoglycemic Agents; D007328:Insulin; D010919:Placebos; D004763:Glucagon-Like Peptides; D005934:Glucagon