Mode of Action of Insulin,Carbutamide,and Tolbutamide. ∗

Abstract

Summary and conclusions

Insulin was injected in different doses and at different rates into either the femoral or the portal vein of anesthetized dogs. No qualitative differences were noted between the 2 routes of administration: in all cases insulin caused a decrease in concentration of blood glucose and potassium and an increase in concentration of pyruvate and lactate. Intravenous carbutamide and tolbutamide caused a decrease not only in blood glucose, and potassium, but also pyruvate and lactate. It is suggested that the drugs may stimulate release of insulin from the pancreas, and that when a minimum (permissive?) amount of insulin is available and glycogenolysis is not accelerated, as in severe diabetes, they may also inhibit glucose production by the liver or its utilization by the muscle. If this hypothesis is correct, prolonged therapy with sulfonylurea-like drugs should be attempted with caution, for continued stimulation of the B cells with sulfonylurea may lead to their exhaustion (1,30) and suppression of hepatic glucose production may be a sign of tissue damage.