TY - JOUR TI - The role of adrenergic mechanisms in the substrate and hormonal response to insulin-induced hypoglycemia in man AU - Garber, A. J. AU - Cryer, P. E. AU - Santiago, J. V. AU - Haymond, M. W. AU - Pagliara, A. S. AU - Kipnis, D. M. T2 - The Journal of Clinical Investigation AB - Sequential determinations of glucose outflow and inflow, and rates of gluconeogenesis from alanine, before, during and after insulin-induced hypoglycemia were obtained in relation to alterations in circulating epinephrine, norepinephrine, glucagon, cortisol, and growth hormone in six normal subjects. Insulin decreased the mean (+/-SEM) plasma glucose from 89+/-3 to 39+/-2 mg/dl 25 min after injection, but this decline ceased despite serum insulin levels of 153+/-22 mul/ml. Before insulin, glucose inflow and outflow were constant averaging 125.3+/-7.1 mg/kg per h. 15 min after insulin, mean glucose outflow increased threefold, but then decreased at 25 min, reaching a rate 15% less than the preinsulin rate. Glucose inflow decreased 80% 15 min after insulin, but increased at 25 min, reaching a maximum of twice the basal rate. Gluconeogenesis from alanine decreased 68% 15 min after insulin, but returned to preinsulin rates at 25 min, and remained constant for the next 25 min, after which it increased linearly. A fourfold increase in mean plasma epinephrine was found 20 min after insulin, with maximal levels 50 times basal. Plasma norepinephrine concentrations first increased significantly at 25 min after insulin, whereas significantly increased levels of cortisol and glucagon occurred at 30 min, and growth hormone at 40 min after insulin. Thus, insulin-induced hypoglycemia in man results from both a decrease in glucose production and an increase in glucose utilization. Accelerated glycogenolysis produced much of the initial, posthypoglycemic increment in glucose production. The contribution of glycogenolysis decreased with time, while that of gluconeogenesis from alanine increased. Of the hormones studied, only the increments in plasma catecholamines preceded or coincided with the measured increase in glucose production after hypoglycemia. It therefore seems probable that adrenergic mechanisms play a major role in the initiation of counter-regulatory responses to insulin-induced hypoglycemia in man. DA - 1976/07// PY - 1976 DO - 10.1172/JCI108460 DP - PubMed VL - 58 IS - 1 SP - 7 EP - 15 J2 - J. Clin. Invest. LA - eng SN - 0021-9738 KW - Adrenergic alpha-Agonists KW - Adult KW - Alanine KW - Epinephrine KW - Glucagon KW - Gluconeogenesis KW - Glucose KW - Growth Hormone KW - Humans KW - Hydrocortisone KW - Hypoglycemia KW - Insulin KW - Kinetics KW - Male KW - Norepinephrine KW - Radioisotope Dilution Technique KW - Sympathetic Nervous System ER -