The Endogenous Glucagon-Like Peptide-1 System is Involved in the Regulation of Fluid Intake
McKay, Naomi J.
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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 influences 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 the physiological control of fluid intake. Accordingly, experiments in this dissertation tested two hypotheses that the GLP-1 system influences fluid intake. First, that endogenous GLP-1 suppresses drinking behavior. Second, that fluid balance affects the endogenous GLP-1 system. Endogenous GLP-1 was blocked with the GLP-1 receptor (GLP-1R) antagonist exendin-9 (Ex-9). Rats that received 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 assessed the response of the GLP-1 system to changes in fluid balance by measuring changes in GLP-1-associated gene expression. It was found that proglucagon and GLP-1R mRNA expression was modified in the ileum, NTS, PVN, and SFO in response to either an osmotic or mixed hypovolemic/osmotic challenge. There were, however, site specific effects. The GLP-1 system within the ileum was altered by access to fluid in a bottle, in the NTS gene expression responded to gastric distention, and in the PVN and SFO GLP-1-associated gene expression was modified by homeostatic state. Overall, these results show a novel association between the endogenous GLP-1 system and fluid intake.