INTERACTION OF EXERCISE, INSULIN, AND HYPOGLYCEMIA STUDIED USING EUGLYCEMIC AND HYPOGLYCEMIC INSULIN CLAMPS

Hyperinsulinemic euglycemic and hypoglycemic clamps were used to study the interaction of exercise, insulin, and hypoglycemia at rest and du ring exercise in the dog. Sampling (artery and portal, hepatic, and il iac veins) and infusion (vena cava) catheters and a flow probe (extern al iliac artery) were implanted surgically >16 days before study. Afte r an 18-h fast and an 80-min tracer equilibration period, dogs were st udied in the basal state (t = -40 to 0 min) and during a moderate trea dmill exercise (t = 0-150 min) period or an equivalent duration sedent ary period. Insulin was infused at 1 mU.kg(-1).min(-1) from t = 0-150 min. In one group of sedentary (n = 7) and one group of exercised (n = 6) dogs, glucose was clamped at basal during the insulin infusion. In another group of sedentary (n = 6) and another group of exercised (n = 6) dogs, arterial glucose was clamped at hypoglycemic levels (simila r to 65 mg/dl) during the insulin infusion. Arteriovenous difference a nd isotopic ([3-H-3]glucose, [U-C-14]glucose) techniques were used to assess glucose metabolism. Insulin levels were similar to 40 mu U/ml i n all groups. Data show that 1) counterregulatory hormone (glucagon, c atecholamines, and cortisol) responses to exercise and hypoglycemia co mbined are synergistically higher than the response to either stimulus alone; 2) exercise-induced increases in insulin action are negated du ring hypoglycemia by the counterregulatory response; 3) decreased need for exogenous glucose during hypoglycemic compared with euglycemic ex ercise is due to stimulation of endogenous glucose production, which a ccounts for similar to 30% of the decrease, and reduction of glucose u tilization, which accounts for similar to 70%; and 4) insulin-stimulat ed nonoxidative glucose metabolism is unaffected by exercise or hypogl ycemia, whereas insulin-stimulated oxidative glucose metabolism is sel ectively increased by exercise and decreased by hypoglycemia. In concl usion, the marked rise in insulin action during exercise is matched, u nder insulin-induced hypoglycemic conditions, by an equally profound i ncrease in counterregulation. The effectiveness of the potent insulin counterregulatory response may be important in decreasing the magnitud e and frequency of exercise-induced hypoglycemia.