ALTERED EPINEPHRINE RESPONSES IN DIABETES

A number of studies have shown that the increase in counterregulatory hormone concentrations induced by hypoglycemia is reduced in insulin-dependent diabetics (IDD's) as compared to nondiabetic controls. In particular, the failure of plasma epinephrine levels to rise normally in IDD's occurs together with the impaired secretion of glucagon. This leads to loss of the acute hormonal response to insulin-induced hypoglycemia which, in turn, results in the lack of rebound in hepatic glucose output posthypoglycemia and delayed recovery to safe blood glucose concentrations. This proposal will study the mechanism underlying the loss of an adequate epinephrine response in IDD's and therapeutic implications of this. Specifically, studies are designed to evaluate the scope of the hormonal abnormality in Type I diabetes in humans by using multiple stimuli to assess secretory responses of epinephrine, glucagon, cortisol, growth hormone, and norepinephrine using non-hypoglycemic and hypoglycemic stimuli. Since preliminary evidence suggests that exercise may potentiate the catecholamine response to hypoglycemia in normal but not diabetic subjects, studies are proposed to explore the relative roles of epinephrine secretion or clearance and the severity of the exercise stimulus in this phenomenon. Experiments in which blood glucose will be held constant during exercise will determine whether the hormone responses to exercise are related to the glucose level, whether their response is still modulated by changes in glucose and whether the defect in epinephrine response is also present in non-insulin dependent diabetes. Finally, the role of epinephrine in exercise-induced glucose production will be evaluated. These studies may help to define the cause(s) of the observed hormonal deficits in IDDM and serve to clarify the role of exercise in the therapy of diabetes.