Endogenous glucagon-like peptide-1 reduces drinking behavior and is differentially engaged by water and food intakes in rats

J Neurosci. 2014 Dec 3;34(49):16417-23. doi: 10.1523/JNEUROSCI.3267-14.2014.


Glucagon-like peptide-1 (GLP-1) is produced in the ileum and the nucleus of the solitary tract. It is well known that GLP-1 controls food intake, but there is a growing literature indicating that GLP-1 also is involved in fluid intake. It is not known, however, if the observed effects are pharmacological or if endogenous GLP-1 and its receptor contribute to physiological fluid intake control. Accordingly, we blocked endogenous GLP-1 by application of a receptor antagonist and measured subsequent drinking. Furthermore, we measured changes in GLP-1-associated gene expression after water intake, and compared the effects of fluid intake to those caused by food intake. Rats injected with the antagonist exendin-9 (Ex-9) drank more fluid in response to either subcutaneous hypertonic saline or water deprivation with partial rehydration than did vehicle-treated rats. Analysis of licking behavior showed that Ex-9 increased fluid intake by increasing the number of licking bursts, without having an effect on the number of licks per burst, suggesting that endogenous GLP-1 suppresses fluid intake by influencing satiety. Subsequent experiments showed that water intake had a selective effect on central GLP-1-related gene expression, unlike food intake, which affected both central and peripheral GLP-1. Although water and food intakes both affected central GLP-1-relevant gene expression, there were notable differences in the timing of the effect. These results show a novel role of the endogenous GLP-1 system in fluid intake, and indicate that elements of the GLP-1 system can be engaged separately by different forms of ingestive behavior.

Keywords: fluid homeostasis; food intake; glucagon-like peptide-1; thirst; water intake.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drinking / drug effects
  • Drinking / physiology*
  • Drinking Behavior / physiology*
  • Eating / physiology*
  • Gene Expression / physiology
  • Glucagon-Like Peptide 1 / antagonists & inhibitors
  • Glucagon-Like Peptide 1 / blood
  • Glucagon-Like Peptide 1 / physiology*
  • Ileum / metabolism
  • Injections, Intraventricular
  • Male
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacology
  • Proglucagon / blood
  • Proglucagon / metabolism
  • Proglucagon / physiology
  • Rats
  • Saline Solution, Hypertonic / pharmacology
  • Solitary Nucleus / drug effects
  • Solitary Nucleus / metabolism
  • Water Deprivation / physiology


  • Peptide Fragments
  • Saline Solution, Hypertonic
  • exendin (9-39)
  • Proglucagon
  • Glucagon-Like Peptide 1