Differential sensitivity of glycogenolysis and gluconeogenesis to insulin infusions in dogs

Abstract

Whether insulin affects gluconeogenesis from alanine in the intact dog was studied, and the effect of insulin on glycogenolysis and gluconeogenesis was compared. In anesthetized dogs fasted overnight, blood samples were drawn simultaneously from a femoral artery and hepatic vein. Alanine-U-14C, 10 .mu.Ci/kg, was infused over 110 min. Constant insulin infusion at either 1 or 5 mU/kg min-1, was begun at 50 min, and blood glucose concentration was maintained by variable glucose infusion. Insulin infusion at 1 mU/kg min-1 resulted in plasma immunoreactive insulin (IRI) levels of 73 .+-. 10 .mu.U/ml, and net splanchnic glucose production (NSGP) was suppressed from 2.7 .+-. 2 mg/kg min-1 to virtually zero. This small increment in insulin concentration had no demonstrable effect on the net splanchnic uptake of alanine or on the conversion of plasma alanine to glucose (7.9 .+-. 0.3 .mu.mol/min). Insulin infused at 5 mU/kg min-1 resulted in IRI levels of 240 .+-. 25 .mu.U/ml. This higher insulin concentration was associated with marked suppression of both the NSGP (100%) and the conversion of plasma alanine to glucose (90%) but did not affect the extraction of alanine by the splanchnic bed. Doses of both 1 and 5 mU/kg min-1 were associated with 35% fall in immunoreactive glucagon levels. These data demonstrate that: glycogenolysis is more sensitive than gluconeogenesis to the inhibitory effect of small increments in insulin concentrations; gluconeogenesis can be suppressed by insulin but only at higher insulin concentrations; this suppression of gluconeogenesis from alanine by insulin was due to an intrahepatic effect rather than an effect on the splanchnic extraction of alanine, and insulin can suppress glucagon in the absence of hyperglycemia.