Epinephrine and the regulation of glucose metabolism: effect of diabetes and hormonal interactions.
Elevations of plasma epinephrine comparable to those observed in physiologic stress, cause a sustained 20--35 mg/dl elevation of plasma glucose in normal humans. This hyperglycemic action is due to a transient increase in hepatic glucose output as well as a reduction in the rate of glucose disposal which accounts for the persistence of hyperglycemia. The latter results from epinephrine-induced suppression of endogenous insulin secretion and, more importantly from a direct inhibitory effect on insulin-stimulated glucose utilization. In diabetes, the hyperglycemic effect of epinephrine is markedly accentuated. The enhanced rise in plasma glucose is due to an alternation in response of the liver to epinephrine. Despite infusion of insulin, epinephrine produces a sustained rather than transient elevation in hepatic glucose output in diabetic subjects. In contrast, the inhibitory effect of epinephrine on glucose utilization is unchanged by the diabetic state. In normal subjects, the hyperglycemic action of epinephrine is enhanced by simultaneous elevations of glucagon and cortisol. The former increases the magnitude, but not the duration, of the rise in hepatic glucose output induced by epinephrine. The latter, converts epinephrine's hepatic action from a transient to a sustained response. Our data thus suggest that marked hyperglycemia in normal subjects requires the concomitant elevation of multiple anti-insulin hormones, whereas such changes may occur in diabetes if any member of this group of hormones is increased. These findings may account for long-standing clinical observation that stress adversely affects blood glucose regulation to a much greater extent in diabetics as compared to normal subjects.
D000328:Adult; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004285:Dogs; D004837:Epinephrine / Q000097:blood / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007657:Ketone Bodies / Q000097:blood; D008099:Liver / Q000187:drug effects; D008657:Metabolic Clearance Rate
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007657:Ketone Bodies; D005934:Glucagon; D006854:Hydrocortisone; D004837:Epinephrine