Gastroenterology

Gastroenterology

Volume 130, Issue 1, January 2006, Pages 44-54
Gastroenterology

Clinical–alimentary tract
Glucagon-Like Peptide 2 Stimulates Glucagon Secretion, Enhances Lipid Absorption, and Inhibits Gastric Acid Secretion in Humans

https://doi.org/10.1053/j.gastro.2005.10.004Get rights and content

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 ∼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.

Section snippets

Study Protocol

The study protocol was approved by the ethics committee of the Ruhr-University of Bochum on March 14th, 2002 (registration number: 1839), prior to the study. Written informed consent was obtained from all participants.

Screening visit

At a screening visit, blood was drawn from all participants in the fasting state for measurements of standard hematologic and clinical chemistry parameters to exclude subjects with anemia (hemoglobin <12 g/dL), an elevation in liver enzymes (alanine amino transferase, aspartate

GLP-2 Plasma Levels

During the exogenous administration of GLP-2 over 120 minutes in the fasting state, plasma levels of intact GLP-2 increased from 10 ± 2 pmol/L to steady-state concentrations of 208 ± 8 pmol/L (P < .001; Figure 1), whereas total GLP-2 levels were raised from 29 ± 6 pmol/L to steady-state levels of 430 ± 17 pmol/L (P < .001; Figure 1).

Following test meal ingestion, total GLP-2 plasma concentrations increased from 17 ± 2 pmol/L to 27 ± 1 pmol/L during placebo administration (P < .001; Figure 2).

Discussion

The present studies were undertaken to investigate the effects of GLP-2 on endocrine pancreatic secretion and postprandial lipid concentrations, as well as on gastric emptying and acid secretion. We report an ∼40%–50% increase in glucagon concentrations, a higher rise in postprandial triglyceride and free fatty acid levels, and an ∼15% reduction in pentagastrin-stimulated gastric acid secretion, whereas insulin plasma concentrations and gastric emptying were virtually unaffected.

The fact that

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