Pancreatic glucagon's effects on satiety and hepatic glucose production are independently affected by diet composition

Abstract

We tested whether pancreatic glucagon's effects on satiety and hepatic glycogenolysis depend on variations in the macronutrient composition of the diet. Rats were kept on high carbohydrate, high fat, or high protein diets (HC-, HF- or HP-rats, respectively) and adapted to a 5 hour feeding (11:00-16:00)-19 hour deprivation (16:00-11:00) schedule. Glucagon (540 mcg/kg body weight) was intraperitoneally injected at 14:00. Glucagon stimulated similar amounts of hepatic glycogenolysis in HC- and in HF-rats and less glycogenolysis in HP-rats, but glucagon decreased food intake only in HC-rats. When HF- or HP-rats were prefed the HC-diet once for 1 hour (11:00-12:00) prior to injection, glucagon stimulated hepatic glycogenolysis similarly in both groups but decreased food intake only in HF-rats. Therefore, stimulation of hepatic glycogenolysis by glucagon is not sufficient to elicit satiety under all feeding conditions. The results also suggest that glucagon-induced satiety is not limited to carbohydrate intake.