A role for glucagon-like peptide-1 in the central regulation of feeding

Nature. 1996 Jan 4;379(6560):69-72. doi: 10.1038/379069a0.


The sequence of glucagon-like peptide-1 (7-36) amide (GLP-1) is completely conserved in all mammalian species studied, implying that it plays a critical physiological role. We have shown that GLP-1 and its specific receptors are present in the hypothalamus. No physiological role for central GLP-1 has been established. We report here that intracerebroventricular (ICV) GLP-1 powerfully inhibits feeding in fasted rats. ICV injection of the specific GLP-1-receptor antagonist, exendin (9-39), blocked the inhibitory effect of GLP-1 on food intake. Exendin (9-39) alone had no influence on fast-induced feeding but more than doubled food intake in satiated rats, and augmented the feeding response to the appetite stimulant, neuropeptide Y. Induction of c-fos is a marker of neuronal activation. Following ICV GLP-1 injection, c-fos appeared exclusively in the paraventricular nucleus of the hypothalamus and central nucleus of the amygdala, and this was inhibited by prior administration of exendin (9-39). Both of these regions of the brain are of primary importance in the regulation of feeding. These findings suggest that central GLP-1 is a new physiological mediator of satiety.

MeSH terms

  • Animals
  • Cerebral Ventricles / physiology*
  • Eating / physiology*
  • Glucagon
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptides
  • Injections, Intraventricular
  • Male
  • Neuropeptide Y / pharmacology
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / pharmacology
  • Peptide Fragments / physiology*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Satiation / physiology


  • Neuropeptide Y
  • Peptide Fragments
  • Proto-Oncogene Proteins c-fos
  • glucagon-like peptide 1 (7-36)amide
  • exendin (9-39)
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon