GLP-1 Regulates Gastroduodenal Motility Involving Cholinergic Pathways

Neurogastroenterol Motil. 2009 Jun;21(6):609-18, e21-2. doi: 10.1111/j.1365-2982.2008.01246.x. Epub 2009 Feb 6.

Abstract

The gut-born incretin hormone glucagon-like peptide-1 (GLP-1) delays gastric emptying. To elucidate the mechanisms by which GLP-1 affects gastroduodenal motility and glycaemia, we studied the effects of exendin(9-39), a potent GLP-1 receptor antagonist, on gastroduodenal motility and pancreatic hormones. In this randomized, double-blind, placebo-controlled, four-arm, cross-over trial, 10 healthy volunteers were studied during the interdigestive period followed by duodenal perfusion of a mixed liquid meal (250 kcal). On four separate days, exendin(9-39), atropine, exendin(9-39) + atropine or saline were infused intravenously. Antro-pyloro-duodenal and fundic motility were assessed. The compliance of the proximal stomach was determined by isobaric distensions. During fasting, exendin(9-39) did not influence proximal gastric volume, pyloric tone, and duodenal contractility. Exendin(9-39) significantly increased antral waves only in the absence of atropine. During duodenal meal perfusion, exendin(9-39) significantly reduced proximal gastric volume accommodation, abbreviated postprandial antral inhibition, reduced the postprandial increase in pyloric tone, and reduced gastric compliance. Atropine abolished the effects of exendin(9-39) on gastric volume accommodation but did not affect its effects on postprandial antroduodenal motility and on gastric compliance. Exendin(9-39) increased fasting and postprandial glycaemia and plasma glucagon but not insulin concentrations. Atropine did not affect GLP-1 secretion. Cholinergic mechanisms mediate the effects of GLP-1 on postprandial gastric accommodation but not on antro-pyloro-duodenal motility. GLP-1 reduces fasting and postprandial glycaemia, in part by reducing glucagon secretion.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atropine / pharmacology
  • Autonomic Pathways / drug effects
  • Autonomic Pathways / physiology*
  • Blood Glucose / metabolism
  • Double-Blind Method
  • Duodenum / drug effects
  • Duodenum / innervation*
  • Duodenum / physiology*
  • Eating / physiology
  • Gastrointestinal Motility / drug effects
  • Gastrointestinal Motility / physiology*
  • Glucagon-Like Peptide 1 / agonists
  • Glucagon-Like Peptide 1 / physiology*
  • Glucagon-Like Peptide-1 Receptor
  • Hormones / blood
  • Humans
  • Male
  • Muscarinic Antagonists / pharmacology
  • Parasympathetic Nervous System / drug effects
  • Parasympathetic Nervous System / physiology*
  • Peptide Fragments / pharmacology
  • Receptors, Glucagon / antagonists & inhibitors
  • Stomach / drug effects
  • Stomach / innervation*
  • Stomach / physiology*

Substances

  • Blood Glucose
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Hormones
  • Muscarinic Antagonists
  • Peptide Fragments
  • Receptors, Glucagon
  • exendin (9-39)
  • Atropine
  • Glucagon-Like Peptide 1