Evidence that intestinal glucagon-like peptide-1 plays a physiological role in satiety.
A physiological role in satiety is proposed for glucagon-like peptide-1 (GLP-1), secreted by the distal intestine in response to ingested nutrients. Here we report that in rats, ip injection of the GLP-1 receptor (GLP-1-R) antagonist exendin 9-39 (Ex9) elicited hyperphagia, but only at times of day when intake is otherwise low. Furthermore, ip administration of Ex9 attenuated satiety induced by either a voluntarily consumed sucrose meal (by 100%) or an intragastric glucose load (by 40%). To determine whether these effects involve blockade of GLP-1-R in brain or at a peripheral site, we injected Ex9 either centrally (into the third ventricle) or peripherally (ip) prior to GLP-1 injected either centrally or peripherally. Anorexia induced by peripheral GLP-1 was fully blocked by peripheral, but not central, pretreatment with Ex9, whereas the opposite was true for anorexic effect of central GLP-1. Thus, ip Ex9 appears to attenuate satiety via peripheral GLP-1-R blockade. Finally, anorexia induced by ip injection of exendin-4 (a GLP-1-R agonist) was due to both reduced meal size and increased duration between meals. We conclude that GLP-1 released from the intestine in response to ingested nutrients is a physiologically active satiety signal.
Williams
Diana L
DL
Department of Psychology, Florida State University, Tallahassee, Florida 32306-4301, USA. williams@psy.fsu.edu
Baskin
Denis G
DG
Schwartz
Michael W
MW
D000818:Animals; D000855:Anorexia / Q000139:chemically induced; D004435:Eating / Q000187:drug effects*; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D007267:Injections; D008297:Male; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors* / Q000502:physiology*; D012528:Satiety Response / Q000187:drug effects*; D014688:Venoms / Q000494:pharmacology
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D000077270:Exenatide