Modulation of food intake by peripherally administered amylin.
Amylin has been demonstrated to produce anorexia in rodents. Its mechanism of action is unknown. We have studied the effect of amylin on food intake in mice in a variety of paradigms to determine whether it inhibits food intake by a peripheral mechanism of action. In addition, we determined its effect in genetically obese mice models and whether its effects differed in aged mice. Cholecystokinin is the prototypic satiety agent. The effects of amylin on reducing food intake were not attenuated by the cholecystokinin antagonist L-364718, suggesting that it does not produce its effect through the release of cholecystokinin. A number of gastrointestinal peptides produce anorexia by stimulating ascending vagal fibers. For this reason, we studied the effect of truncal vagotomy on the suppression of feeding induced by amylin. Vagotomy did not prevent amylin from inhibiting food intake. Amylin was equally effective at reducing food intake in genetically obese (ob/ob) and lean (ob/c) mice and in diabetic (db/db) and lean (db/c) mice. Amylin effectively suppressed food intake in mice over the age of 4-22 mo. These studies further support the role of the pancreatic hormone amylin as a peripherally acting satiety agent.
Morley
J E
JE
Geriatric Research Education and Clinical Center, Department of Veterans Affairs Medical Center, St. Louis, Missouri.
Flood
J F
JF
Horowitz
M
M
Morley
P M
PM
Walter
M J
MJ
D000682:Amyloid / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D020109:Devazepide; D003920:Diabetes Mellitus / Q000235:genetics; D004435:Eating / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D058228:Islet Amyloid Polypeptide; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009765:Obesity / Q000235:genetics; D012844:Sincalide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014628:Vagotomy
D000682:Amyloid; D001570:Benzodiazepinones; D058228:Islet Amyloid Polypeptide; D020109:Devazepide; D012844:Sincalide