Mechanism of Insulin Hypersensitivity in the Hypophysectomized Dog

Abstract

Following the intravenous injection of glucagon-free insulin into unanesthetized hypophysectomized dogs in the postabsorptive state, changes in the rates of glucose outflow from the plasma into the tissues and glucose inflow into the plasma from the liver were determined. By the use of C¹⁴ glucose, these flow rates were determined simultaneously while the plasma glucose concentration was changing. In the hypophysectomized dog, the same amount of insulin caused a greater increase in outflow from the plasma than in the normal dog, the duration of the period of increased outflow was not significantly longer. The liver of the hypophysectomized dog failed to release enough glucose in response to the induced hypoglycemia to restore the plasma glucose concentration promptly to the preinsulin level, whereas the liver of the normal dog responded readily. Because of the greater outflow of plasma glucose and inadequate inflow of glucose and the lower initial plasma glucose concentration, insulin causes a more severe and prolonged hypoglycemia in the hypophysectomized animal. The insulin hypersensitivity of the hypophysectomized dog may thus be attributed to two separate and perhaps equally important factors: a) a small amount of injected insulin results in a greater increase in the rate of plasma glucose uptake by the tissues than in the normal animal, and b) the hypoglycemia in the hypophysectomized dog is less effective in bringing about the release of sufficient amounts of glucose by the liver than in the normal one.