The satiating potency of hepatic portal glucagon in rats and insulin or insulin antibodies

To characterize the interactive effects of acute prandial manipulations of insulin and glucagon on spontaneous feeding in adult male rats fed ad lib, glucagon (G) and insulin (I) or insulin antibodies (IAb) were coinfused into the hepatic portal vein during the first meal of the dark phase. Infusions (3-6 min, 33 mu l/min) were remotely controlled, and a computerized system recorded meal patterns. In Experiment 1, five separate factorial designs were used to test the effects of G (1.3 or 13 mu g/meal) alone, I (1.3 or 2.7 mU/meal) alone, or both G + I. The peptides were infused either simultaneously or sequentially (G before I). The larger dose of G alone reduced meal size. I neither inhibited feeding nor increased the effects of either G dose. In one test, 13 mu g/meal G did not block meal size when followed by 2.7 mU I, but this antagonism did not occur in a replication. In several tests, there was a trend for I to decrease the size of the spontaneous meal that followed the meal during which I was infused, but this was statistically significant only once. Intermeal intervals were not affected in any test. Experiment 2 tested coinfusions of 20 mu g G and polyclonal IAb with an in vitro binding capacity of 40 mU rat insulin. G alone reduced meal size, IAb alone increased meal size, and G + IAb produced an additive effect. These data extend previous investigations of the satiating action of G and I in the rat and indicate 1. that exogenous I does not affect the satiating potency of G; 2. that exogenous G and endogenous I elicit an additive synergistic inhibition of spontaneous meal size; and 3, that G-induced I secretion does not mediate the satiating effect of G. Copyright (C) 1997 Elsevier Science Inc.