Central administration of GLP-1-(7-36) amide inhibits food and water intake in rats.
Glucagon-like peptide (GLP)-1-(7-36) amide and its pancreatic receptors are important for control of blood glucose levels. However, rat GLP-1 receptors are also localized in the brain, in hypothalamus, and in areas without a blood-brain barrier. When rats were kept on a food restriction schedule, intracerebroventricular injection of GLP-1 just before food was offered inhibited food intake. However, peripheral GLP-1 administration by intraperitoneal injection had little effect. GLP-1 effects on water intake and output were also investigated. Intracerebroventricular GLP-1 profoundly inhibited angiotensin II-induced drinking behavior in rats, and water intake was suppressed by exogenous GLP-1 in rats habituated to a water restriction schedule. These effects were reproduced by intraperitoneal administration of GLP-1. Furthermore, intracerebroventricular GLP-1 stimulated urinary excretion of water and sodium. The centrally elicited effects were blocked by the GLP-1 antagonist exendin-(9-39) amide, whereas the N-terminally extended and inactive GLP-1-(1-36) amide had no effect on feeding and drinking. GLP-1 had no effect in behavioral assays measuring exploratory locomotor activity and conditioned taste aversion. In conclusion, GLP-1 may play a physiological role in regulation of both ingestion and the water and salt homeostasis.
Department of Clinical Biochemistry 7642, State University Hospital of Copenhagen, Denmark.
M
M
Tang-Christensen
P J
PJ
Larsen
R
R
Göke
A
A
Fink-Jensen
D S
DS
Jessop
M
M
Møller
S P
SP
Sheikh
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000502:physiology*; D004326:Drinking / Q000187:drug effects*; D004435:Eating / Q000187:drug effects*; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D007276:Injections, Intraventricular; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D010446:Peptide Fragments; C055453:glucagon-like peptide 1 (7-36)amide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon