Mode of Action of Insulin, Carbutamide, and Tolbutamide.

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Abstract
Insulin was injected in different doses and at different rates into the femoral or portal vein of anesthetized dogs. No qualitative differences were noted between the two routes of administration: in all cases insulin caused a decrease in the concentration of blood glucose and K and an increase in the concentration of pyruvate and lactate. Intravenous carbutamide and tolbutamide caused a decrease not only in blood glucose, and K, but also pyruvate and lactate. It is suggested that the drugs may stimulate the 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 sulfanylurea-like drugs should be attempted with caution, for the continued stimulation of the B cells with sulfonylurea may lead to their exhaustion and the suppression of hepatic glucose production may be a sign of tissue damage.