Studies on the mechanism of epinephrine-induced hyperglycemia in man. Evidence for participation of pancreatic glucagon secretion.
In man, epinephrine induces increases in plasma levels of glucagon, a lipolytic and hyperglycemic hormone. To determine glucagon's contribution to this hyperglycemia and lipolysis, the effects of inhibition of pancreatic alpha-cell responses to epinephrine were investigated with somatostatin and adrenergic receptor blockade. To avoid ambiguities that might result from concomitant changes in endogenous insulin secretion, these studies were performed in juvenile-type, insulin-deficient diabetic subjects. Compared with normal subjects, the diabetics had excessive glucagon responses to epinephrine, which had been infused to attain circulating levels within the range found in man in severe stress. Both somatostatin and propranolol completely prevented glucagon responses and diminished the glycemic response to epinephrine by 40 to 50 per cent. Free fatty acid responses to epinephrine were completely prevented by propranolol but unaffected with somatostatin. Phentolamine had no effect on glucose, free fatty acid, or glucagon responses to epinephrine. These studies demonstrate that epinephrine, via a beta-adrenergic receptor mechanism, causes excessive plasma glucagon elevation in human diabetes mellitus and indicate that this hyperglucagonemia participates in the hyperglycemic, but not the lipolytic, response to epinephrine. Catecholamine-induced hyperglucagonemia may thus provide an additional explantation for the deterioration in carbohydrate tolerance associated with stress.
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000503:physiopathology*; D004357:Drug Synergism; D004837:Epinephrine; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced* / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D013004:Somatostatin; D005934:Glucagon; D011433:Propranolol; D004837:Epinephrine; D010646:Phentolamine