Comparative effects of amylin and cholecystokinin on food intake and gastric emptying in rats

Abstract

CCK is a physiological inhibitor of gastric emptying and food intake. The pancreatic peptide amylin exerts similar actions, yet its physiological importance is uncertain. Objectives were to compare the dose-dependent effects of intravenous infusion of amylin and CCK-8 on gastric emptying and food intake in rats, and to assess whether physiological doses of amylin are effective. Amylin and CCK-8 inhibited gastric emptying with mean effective doses (ED(50)s) of 3 and 35 pmol x kg(-1) x min(-1) and maximal inhibitions of 60 and 65%, respectively. Amylin and CCK-8 inhibited food intake with ED(50)s of 8 and 14 pmol x kg(-1) x min(-1) and maximal inhibitions of 78 and 69%, respectively. The minimal effective amylin dose for each effect was 1 pmol x kg(-1) x min(-1). Our previous work suggests that this dose increases plasma amylin by an amount comparable to that produced by a meal. These results support the hypothesis that amylin acts as a hormonal signal to the brain to inhibit gastric emptying and food intake and that amylin produces satiety in part through inhibition of gastric emptying.

Ghrelin Attenuates the Inhibitory Effects of Glucagon-Like Peptide-1 and Peptide YY(3-36) on Food Intake and Gastric Emptying in Rats

“…Bolus administration of ghrelin to rodents during the dark period, their active feeding period, has been reported to produce little if any effect on food intake (9 -12). Our previous work suggests that intravenous infusion of the anorexigenic peptides CCK-8, amylin, PYY , and GLP-1 during the early dark period produces a more potent and reliable suppression of feeding in rats than bolus administration (3)(4)(5)(6). No previous study has exam- ined the effects of intravenous infusion of ghrelin under these conditions.…”

“…We have provided evidence that CCK, GLP-1, PYY , and amylin may inhibit food intake in part by inhibiting gastric emptying because each peptide dose-dependently reduces food intake and gastric emptying with similar potency and efficacy in rats (3)(4)(5)(6). Ghrelin has been reported to stimulate both gastric emptying and food intake (2,7,8).…”

“…Our previous work with anorexigenic peptides suggests that intravenous infusion of these peptides in rats during the early dark period produces a more potent and reliable suppression of feeding than bolus administration (3)(4)(5)(6). The effects of intravenous infusion of ghrelin under these conditions remain to be determined.…”

Comparison of the inhibitory effects of PYY(3-36) and PYY(1-36) on gastric emptying in rats

“…Our results also suggest that hPYY(3-36) and rPYY , which differ by two amino acids at positions 3 and 18 (20,28), inhibit gastric emptying in rats with a similar potency and efficacy. We have used the same experimental model to determine the dose-dependent effects of CCK-8, amylin, calcitonin (CT), salmon CT (sCT), CT-gene-related peptide (CGRP), and adrenomedullin (ADM) on gastric emptying (41,42). Our results suggest an order of potency of sCT Ͼ amylin Ͼ CCK-8 ϭ PYY(3-36) Ͼ CGRP ϭ ADM Ͼ PYY(1-36) Ͼ CT (estimated ED 50 s are 1, 3, 35, 37, 130, 160, 470, and 730 pmol⅐kg Ϫ1 ⅐min Ϫ1 , respectively).…”

Gut hormones such as amylin and GLP-1 in the control of eating and energy expenditure

“…One important criterion is that the meal-contingent infusion of amylin into the portal vein dose-dependently reduced the size and duration of the ongoing meal, and that the onset of this action occurred within minutes after administration. 2 The meal size effect of amylin appeared to be independent of the route of administration (for example, Reidelberger et al, 20 Reidelberger et al 21 and Rushing et al 22 ), and similar observations have also been reported for GLP-1. 23,24 Administration of the amylin antagonist AC187 increased meal size, 25 underlining the physiological relevance of amylin's effect.…”