Food deprivation dissociates pancreatic glucagon's effects on satiety and hepatic glucose production at dark onset

Abstract

We compared the effects of different durations of pretest food deprivation on pancreatic glucagon's (PG) satiating and glycogenolytic actions in order to test the hypothesis that stimulation of hepatic glucose production causes PG's satiety effect. Rats were maintained on a 12:12 LD cycle (lights off: 1015) and deprived of food 45 min or 8, 12, 18, or 24 hr before intraperitoneal injection of 400 μg/kg PG. Testing began at 1015, the beginning of the dark phase. Food intake was not inhibited after 45 min of pretest food deprivation (30 min change, 2.5±4.0%, p<0.05), but was inhibited after 8 or more hr food deprivation. The largest inhibitory effect, 16.2±3.8%, p<0.01, occurred after 8 hr food deprivation. In separate experiments, rats were food deprived 45 min or 8 hr, similarly injected, and killed 10 min after refeeding for blood and liver samples. Hepatic glycogen content at meal onset was higher in rats deprived 45 min than in rats deprived 8 hr ( 3.2±0.3 vs. 1.7±0.3% liver weight, p<0.01), and PG injection produced a higher level of hepatic vein blood glucose in the less deprived rats ( 196±5 vs. 168±12 mg/dl, p<0.05). Thus, in rats tested at the beginning of the dark phase of the LD cycle after 45 min or 8 hr food deprivation, there is an inverse relation between PG's potencies to inhibit food intake and to stimulate hepatic glucose production. We conclude that PG's glycogenolytic effect does not account for its effects on meals in 0–8 hr food deprived rats tested at the beginning of the dark phase of the circadian cycle.