Central insulin enhances sensitivity to cholecystokinin

Insulin acts in the brain to reduce food intake and body weight. Cholecystokinin (CCK) reduces meal size when administered peripherally. The purpose of these experiments was to examine their interaction. In Experiment 1, Long-Evans rats were infused with vehicle or insulin at doses from 0.5 to 2.0 mU/day into the third cerebral ventricles. Doses of 1.0 mU/day and higher caused reduced body weight. A dose of 0.5 mU/day was therefore taken to be subthreshold. In Experiment 2, rats receiving 0.5 mU/day of insulin intracerebroventricularly had greater suppression of 30-min meal size in response to intraperitoneal CCK-8 at doses from 0.25 to 8 mg/kg than did rats receiving intracerebroventricular saline. By itself, the insulin had no effect on body weight or meal size. However, a change of sensitivity to CCK by control rats over the course of the experiment clouded the interpretation. A third experiment was therefore conducted in which rats received an acute intracerebroventricular injection of insulin (0.1 mU) or saline 1 h prior to a 30-min meal, and IP CCK-8 (4 mg/kg) or saline immediately prior to the meal. As in Experiment 2, insulin, itself, had no effect on meal size but enhanced the anorexic effect of CCK. These results are consistent with the hypothesis that central insulin acts by altering sensitivity to satiety agents.