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

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.