Important role of adrenergic mechanisms in acute glucose counterregulation following insulin-induced hypoglycemia in type I diabetes. Evidence for an effect mediated by beta-adrenoreceptors.
During hypoglycemia induced by an i.v. insulin infusion for 60 min, rates of plasma glucose (PG) decrease and recovery, PG nadir, and plasma counter-regulatory hormone and free fatty acid responses were studied in eight type I uncomplicated diabetic subjects and eight nondiabetic subjects. Each subject was tested three times at two different rates of insulin infusion (25 and 32 mU/m2/min): (1) during infusion of saline, (2) during infusion of phentolamine + propranolol (combined alpha, beta-blockade), and (3) during infusion of propranolol alone (isolated beta-blockade) for 150 min. At the time of the studies, the diabetic subjects had been made euglycemic by an overnight i.v. insulin infusion. During infusion of insulin (25 mU/m2/min) and saline, the rates of PG decrease and recovery were slower (P less than 0.01) and PG nadir was delayed in the diabetic subjects. Moreover, their plasma glucagon response was blunted while plasma epinephrine, norepinephrine, growth hormone, and cortisol responses were similar in both groups. Infusion of insulin at 32 mU/m2/min caused larger decreases in PG than had been observed when insulin was infused at 25 mU/m2/min. Plasma glucagon responses increased in the nondiabetic subjects (P less than 0.05) but not in the diabetic subjects. However, in the diabetic subjects, plasma epinephrine increased more than in the nondiabetic subjects (P less than 0.05). There was an inverse correlation between the individual plasma epinephrine responses and the plasma glucagon responses in the diabetic subjects (r = -0.72) but not in the nondiabetic subjects. Alpha, beta-adrenergic blockade decreased the plasma glucose nadir and impaired the rate at which normoglycemia was restored in the diabetic subjects (P less than 0.005 vs. saline) but not in the nondiabetic subjects. Plasma catecholamine and growth hormone responses were increased and plasma FFA recovery was suppressed in both groups (P less than 0.05 vs. saline), while the cortisol responses were unaltered. During isolated beta-adrenergic blockade, changes in plasma glucose, counterregulatory hormones and FFA were essentially identical to those observed during combined alpha, beta-adrenergic blockade in both groups except that the augmented plasma norepinephrine responses were no longer apparent.


CONCLUSIONS
although epinephrine is not essential for prompt restoration of normoglycemia in normal man following insulin-induced hypoglycemia, it plays a major role in glucose counterregulation in diabetics who have an impaired glucagon secretion in response to hypoglycemia. These counterregulatory effects of epinephrine are mediated by beta-adrenoreceptors.
D001786:Blood Glucose / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000097:blood*; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000097:blood* / Q000139:chemically induced; D007328:Insulin / Q000008:administration & dosage; D009638:Norepinephrine / Q000097:blood; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D013006:Growth Hormone; D005934:Glucagon; D011433:Propranolol; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine