CHRONIC INTRAHYPOTHALAMIC INFUSIONS OF INSULIN OR INSULIN-ANTIBODIES ALTER BODY-WEIGHT AND FOOD-INTAKE IN THE RAT

In Experiment 1, one-week infusion of insulin (0.15, 1.5, or 15.0-mu-U/hr) into the ventromedial hypothalamus (VMH) of rats reduced body weight (BW) and nighttime food intake (FI). While 0.15-mu-U/h decreased daytime FI, 1.5-mu-U/h increased daytime FI and 15.0-mu-U/h left daytime FI unchanged. Total daily FI was decreased by the two highest doses. In Experiment 2. intra-VMH infusion of specific insulin antibodies (1.5-mu-Ueq/h) increased BW and Fl, while C-peptide antibodies were ineffective. In Experiment 3a, intracerebroventricular infusions of insulin failed to decrease Fl and BW comparably to similar intrahypothalamic infusions. In Experiment 3b, intra-VMH insulin was infused via cannulae that bypassed the cerebral ventricles. The decrease in FI and BW was comparable to that observed when insulin was infused via cannulae that penetrated a ventricle. Histology from animals used in Experiments 1-3 indicates that optimum sites for insulin-induced changes in BW and FI in the hypothalamus lie in an area that includes portions of the paraventricular, arcuate, dorsomedial. and ventromedial nuclei.