Stimulation of insulin release and suppression of feeding by hepatic portal glucagon infusion in rats.

Plasma insulin and glucose concentrations were measured in rats by remote blood sampling techniques 5 and 25 min after the start of a continuous intraportal glucagon infusion (0.33, 1.0, 3.3, 10 and 33 micrograms/kg/min). Plasma insulin levels were elevated in a dose-related fashion by glucagon, with the highest dose producing a 23-fold increase above control levels. In contrast, the glycemic effect of glucagon was not dose-related. Glucagon-induced hyperglycemia was similar for all glucagon doses, despite the fact that a glucagon dose range spanning two orders of magnitude was used. In a second experiment, plasma glucose and insulin were measured as described above at two glucagon infusion rates (1 and 10 micrograms/kg/min), but the animals were allowed to eat during the infusion. Results showed that the effects of glucagon infusions on plasma insulin and glucose were additive with the normal prandial changes in these substances. Finally, food intake was inversely related to insulin level and dissociated from the hyperglycemia during glucagon infusion. These results show that exogenous glucagon provides a potent stimulus for insulin release in the rat both in the presence and in the absence of food. Furthermore, these results in combination with other data suggest that glucagon-induced hyperinsulinemia merits further investigation as one possible determinant of glucagon satiety in the rat.