PHYSIOLOGICAL-CHANGES IN CIRCULATING GLUCAGON ALTER HEPATIC GLUCOSE DISPOSITION DURING PORTAL GLUCOSE DELIVERY

This study examined whether physiological changes in glucagon alter ne t hepatic glucose uptake (NHGU) or glycogen synthesis under conditions of hyperglycemia, hyperinsulinemia, and portal vein glucose concentra tions exceeding those in the arterial circulation. Somatostatin was in fused into 42-h-fasted dogs, insulin and glucagon were replaced intrap ortally at basal rates, and peripheral infusion of glucose maintained the hepatic glucose load twofold basal for 90 min (period 1). In perio d 2 (240 min) the insulin infusion was increased fourfold, glucose was infused intraportally, the hepatic glucose load was twofold basal, an d glucagon was infused to create levels 150% basal (HiGGN, n = 6) or 4 0% basal (LoGGN, n = 6). NHGU rates (mg.kg(-1).min(-1)) were low durin g period 1 (-0.9 +/- 0.7 in LoGGN and -0.2 +/- 0.4 in HiGGN, not signi ficant) but increased during period 2 (-4.1 +/- 0.6 in LoGGN and -1.9 +/- 0.2 in HiGGN, P < 0.05). Endogenous glucose production (Endo R-a) declined during period 2 in LoGGN (P < 0.01 vs. basal) but did not; ch ange in HiGGN. Tracer-determined hepatic glucose uptake did not differ between groups. The poststudy increment in liver glycogen synthase I (12.5 +/- 3 vs. 6.5 +/- 2% of total) was greater in LoGGN (P < 0.05), as was net glycogen synthesis (27 +/- 8 vs. 13 +/- 3 mg/g liver, P = 0 .06). An elevation in glucagon reduced NHGU (because of failure to sup press Endo R,) and glycogen synthase activation and tended to reduce g lycogen deposition.