Resistance of the obese Zucker rat to insulin-induced feeding and to satiety induced by coinfusion of insulin and glucose.

In normal rats, hypoglycemic doses of intravenous insulin bring about glucoprivic feeding but the same doses of insulin inhibit feeding when combined with doses of glucose that prevent hypoglycemia. In this study, these effects were compared between obese Zucker rats (fa-fa), known to present several abnormalities related to insulin, and normal Wistar rats by infusion of insulin (1 IU over 1 h), insulin plus glucose (5.1 g over 2 h) or vehicle. Feeding patterns and microstructure were automatically monitored. Contrary to its effect in the normal rats, insulin infusion did not enhance feeding in the Zucker rats but rather slightly decreased total food intake and meal duration. The insulin plus glucose infusion produced a total anorexia in normal rats but only a partial reduction in total food intake and meal duration was observed in Zucker rats. The impaired feeding effect of insulin in the Zucker rat may be related to its peripheral resistance to insulin which prevents a severe hypoglycemia and therefore glucoprivic feeding. The lack of inhibition of feeding when both insulin and glucose are infused may account for the well-known delayed satiation and large meals in the Zucker rats, possibly involving impaired hypothalamic action of insulin.