Failure of pulsatile infusion to increase glucagon's satiating potency

Abstract

Intraportal infusions of glucagon elicit a dose-related reduction in the size of rats' spontaneous meals. The glucagon doses required to reduce meal size, however, appear large in comparison to plasma glucagon concentrations during meals. Because prandial glucagon secretion may be pulsatile, however, pulsatile glucagon infusions may reduce meal size more potently than continuous infusions. To test that hypothesis, I compared the effects of a single 2-min infusion of 6.8 μg/min glucagon and two 1-min pulses of the same glucagon concentration separated by 1 min. Glucagon was infused via the hepatic portal vein during male rats' first spontaneous meal of the last quarter of the dark phase, and meal patterns were recorded by a computer. The results did not support the hypothesis. Meal size was reduced comparably in each infusion condition (from ∼3.1 g in the control conditions to ∼2.3 g after continuous glucagon infusion and ∼2.2 g after pulsatile infusion). This result is discussed in relation to tests of glucagon antibody administration that indicate endogenous glucagon is a physiological control of meal size in rats. Additionally, in contrast to previous reports, glucagon infusion during late dark spontaneous meals decreased the length of the subsequent intermeal intervals, suggesting that glucagon's satiating effect was transient.