Dr. Shamoon has shown that, in contrast to the findings in normals, insulin treated juvenile-onset diabetics exhibited exaggerated hepatic responses to cortisol and epinephrine. He will now examine whether: (1) alterations in the hepatic response to cortisol and epinephrine in diabetes are the result of exaggerated gluconeogenesis induced by these hormones; (2) cortisol sustains glucose production induced by epinephrine in normal man by enhancing it gluconeogenic effects; and (3) whether altered sensitivity to epinephrine in diabetes is due to changes in the response of the liver to Alpha or Beta-adrenergic stimulation. Infusions of physiologic doses of cortisol and epinephrine will be carried out in normal and diabetic subjects. Glucose and gluconeogenic precursor tracers will be infused to quantitate hepatic glucose production and conversion of substrates into glucose (gluconeogenesis). Diabetics will be studied during insulin infusion, after normalization of the plasma glucose, to exclude the effects of insulin deficiency per se. Selective Alpha and Beta antagonists will be infused in order to determine whether hypersensitivity to epinephrine is mediated by altered Alpha- or Beta-adrenergic responsiveness in diabetes. These studies are designed to clarify the pathogenesis of stress-induced diabetes in normal man and the mechanism underlying the propensity of even the well-controlled diabetic to develop severe hyperglycemia during minor illness.
