Glucagon-like peptide-1 inhibits gastric emptying via vagal afferent-mediated central mechanisms

Am J Physiol. 1997 Oct;273(4):G920-7. doi: 10.1152/ajpgi.1997.273.4.G920.


Exogenous administration of glucagon-like peptide-1-(7-36) amide (GLP-1), an insulinotropic hormone, inhibits gastric emptying and acid secretion in humans. The role of GLP-1 as a regulator of gastric function is elusive. In gastric fistula rats, vagal afferent denervation and peripheral administration of the GLP-1 receptor antagonist exendin-(9-39) amide enhanced emptying of a glucose meal, whereas intracerebroventricular exendin was ineffective. The rate of saline emptying was attenuated by peripheral as well as by central administration of GLP-1, and pretreatment with exendin by the respective routes reversed the inhibition by GLP-1. Vagal afferent denervation abolished the central and peripheral action of GLP-1 on gastric emptying. Neither peripheral cholinergic nor adrenergic blockade altered the delay of methyl cellulose meal emptying by intracisternal GLP-1 injection. Acid secretion in conscious pylorus-ligated rats was inhibited by intracisternal GLP-1 administration, whereas systemic GLP-1 was ineffective. These results support the notion that GLP-1 receptors participate in the central and peripheral regulation of gastric function. Furthermore, vagal afferent nerves mediate the inhibitory action of GLP-1 on gastric motor function. GLP-1 may be a candidate brain-gut peptide that acts as a physiological modulator of gastric function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Capsaicin / pharmacology
  • Cerebral Ventricles / drug effects
  • Cerebral Ventricles / physiology*
  • Denervation
  • Female
  • Gastric Acid / metabolism*
  • Gastric Emptying / drug effects
  • Gastric Emptying / physiology*
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / physiology*
  • Gastrointestinal Hormones / pharmacology
  • Glucagon-Like Peptide 1
  • Glucose / metabolism
  • Injections, Intraventricular
  • Peptide Fragments / pharmacology
  • Peptides / administration & dosage
  • Peptides / blood
  • Peptides / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Stomach / innervation
  • Vagus Nerve / drug effects
  • Vagus Nerve / physiology*
  • Venoms / pharmacology
  • Visceral Afferents / drug effects
  • Visceral Afferents / physiology*


  • Blood Glucose
  • Gastrointestinal Hormones
  • Peptide Fragments
  • Peptides
  • Venoms
  • exendin (9-39)
  • Glucagon-Like Peptide 1
  • Glucose
  • Capsaicin