Does neuropeptide Y contribute to the anorectic action of amylin?
Neuropeptide Y (NPY) is a potent feeding stimulant acting at the level of the hypothalamus. Amylin, a peptide co-released with insulin from pancreatic beta cells, inhibits feeding following peripheral or central administration. However, the mechanism by which amylin exerts its anorectic effect is controversial. This study investigated the acute effect of amylin on food intake induced by NPY, and the effect of chronic amylin administration on food intake and body weight in male Sprague Dawley rats previously implanted with intracerebroventricular (icv) cannulae. Rats received 1 nmol NPY, followed by amylin (0.05, 0.1, 0.5 nmol) or 2 microl saline. Increasing doses of amylin resulted in a dose-dependent inhibition of NPY-induced feeding by 31%, 74% and 99%, respectively (P < 0.05). To determine the chronic effects of i.c.v. amylin administration on feeding, rats received 0.5 nmol amylin or saline daily, 30 min before dark phase, over 6 days. Amylin significantly reduced food intake at 1, 4, 16 and 24 hours; after 6 days, amylin-treated rats showed a significant reduction in body weight, having lost 17.3 +/- 6.1 g, while control animals gained 7.7 +/- 5.1 g (P < 0.05). Brain NPY concentrations were not elevated, despite the reduced food intake, suggesting amylin may regulate NPY production or release. Thus, amylin potently inhibits NPY-induced feeding and attenuates normal 24 hour food intake, leading to weight loss.
Morris
M J
MJ
Department of Pharmacology, The University of Melbourne, Melbourne, Australia. mjmorris@unimelb.edu.au
Nguyen
T
T
D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001067:Appetite Depressants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005247:Feeding Behavior / Q000187:drug effects; D058228:Islet Amyloid Polypeptide; D008297:Male; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000682:Amyloid; D000897:Anti-Ulcer Agents; D001067:Appetite Depressants; D058228:Islet Amyloid Polypeptide; D009478:Neuropeptide Y