Elsevier

Physiology & Behavior

Volume 64, Issue 4, 15 June 1998, Pages 557-561
Physiology & Behavior

Original Articles
Synergy between amylin and cholecystokinin for inhibition of food intake in mice

https://doi.org/10.1016/S0031-9384(98)00110-3Get rights and content

Abstract

BHAVSAR, S., J. WATKINS AND A. YOUNG. Synergy between amylin and cholecystokinin for inhibition of food intake in mice. PHYSIOL BEHAV 64(4) 557–561, 1998.—Several gastrointestinal peptides which are secreted in response to nutrients have been reported to suppress food intake. Amylin is a peptide hormone co-secreted with insulin from pancreatic β-cells in response to nutrient stimuli. Cholesystokinin (CCK) is secreted from duodenal and jejunal mucosal cells in response to fat and protein. Amylin and CCK-8 have been reported to reduce food intake in rodents when given centrally as well as peripherally. Amylin injected intraperitoneally (i.p.) reduced food intake over the subsequent 30 min in overnight fasted mice by a maximum of 57 ± 6% with an ED50 of 0.93 nmol/kg (3.63 μg/kg) ± 0.34 log units. On a molar basis, this potency was similar to that of CCK-8 (ED50 0.85 nmol/kg (0.97 μg/kg) ± 0.28 log units; p = 0.93) which inhibited food intake by a maximum of 71 ± 7%. When amylin and CCK-8 were injected i.p. as an amylin:CCK-8 mixture, immediately before presentation of food in overnight fasted mice, food intake in the subsequent 30 min was reduced by a maximum of 91%, an amount that was greater than that producable by i.p. injection of amylin or CCK-8 alone. Isobolar analysis revealed a marked synergy between amylin and CCK-8 in reducing food intake, such that statistically ineffective doses of amylin and CCK, when combined, evoked near-maximal inhibition of food intake. Because the typical physiological event is for amylin and CCK both to be secreted in response to mixed meals, the synergy between them could indicate a shared role in physiological appetite control.

Section snippets

Animals

Male Swiss–Webster (NIH-Swiss) mice (n = 378) obtained from Harlan (Madison, WI, USA) at 6 to 8 weeks of age were housed in groups of four. Body mass was 29.3 ± 1.9 g (mean ± SD) at the time of experiments. Mice had ad lib. access to water and food pellets (Teklad LM 485, Madison, WI, USA) and were maintained in an environment of 22 ± 1°C, 60 ± 10% relative humidity, 12:12 light:dark cycle (lights on at 0600 hours) for at least 1 week before experiments. All experiments were conducted between

Food intake after injection with amylin or CCK-8 alone

Amylin and CCK-8 each inhibited 30-min food intake in overnight-fasted NIH-Swiss mice in a sigmoid dose-dependent manner (Goodness of fit r2 = 0.996, 0.997, respectively).

Amylin, at the highest dose tested (25.5 nmol/kg; 100μg/kg i.p.), reduced food intake by 57.0 ± 5.6% (p < 0.01 cf. saline injected controls). The ED50 for amylin-inhibition of food intake was 0.93 nmol/kg (3.63 μg/kg) ± 0.34 log units. The least effective dose of amylin (the lowest dose producing a response different from

Discussion

We have shown that both amylin and CCK-8 dose-dependently inhibit food intake in the overnight fasted mice, when injected i.p., confirming previous reports that these peptides reduce food intake. CCK, which circulates in man at concentrations of 1–7 pm (19), is proposed to be an endogenous peripheral satiety agent. Some (25) have argued that amylin, which circulates at concentrations of 5–25 pm (28) could also function, in part, as an endogenous satiety agent.

Amylin’s action to inhibit gastric

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