Regulation of blood glucose concentration: hepatic action of insulin

¹ Departments of Biochemistry, Medicine, and Surgery, School of Medicine, Western Reserve University, Cleveland, Ohio

Insulin was administered intravenously with or without the concurrent infusion of glucose to dogs surgically prepared so that hepatic glucose production could be measured directly. In dogs fed a high protein diet, hepatic glucose output as directly measured did not significantly change on insulin administration. The threshold at which a net hepatic glucose uptake occurred on the administration of a glucose load was unaffected by the presence of insulin. In contrast, in dogs fed a high carbohydrate diet, on the simultaneous infusion of insulin and glucose, a net uptake of glucose by the liver occurred at lower than normal plasma glucose concentrations. Hepatic glucose production was also estimated indirectly by isotopic techniques. A brief decrease in the rate of decline of plasma glucose specific activity was observed following the injection of C¹⁴-labeled glucose and then insulin in both protein and carbohydrate-fed animals. The explanation for this phenomenon remains uncertain. It is concluded that dietary status is important in determining the action of insulin on the liver. In dogs fed a high carbohydrate diet an almost immediate and perhaps direct action of insulin on the liver appears demonstrable.