Interaction of exercise, insulin, and hypoglycemia studied using euglycemic and hypoglycemic insulin clamps

Abstract

Hyperinsulinemic euglycemic and hypoglycemic clamps were used to study the interaction of exercise, insulin, and hypoglycemia at rest and during exercise in the dog. Sampling (artery and portal, hepatic, and iliac veins) and infusion (vena cava) catheters and a flow probe (external iliac artery) were implanted surgically >16 days before study. After an 18-h fast and an 80-min tracer equilibration period, dogs were studied in the basal state (t = -40 to 0 min) and during a moderate treadmill exercise (t = 0-150 min) period or an equivalent duration sedentary period. Insulin was infused at 1 mU x kg(-1) x 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 (approximately 65 mg/dl) during the insulin infusion. Arteriovenous difference and isotopic ([3-(3)H]glucose, [U-(14)C]glucose) techniques were used to assess glucose metabolism. Insulin levels were approximately 40 microU/ml in all groups. Data show that 1) counterregulatory hormone (glucagon, catecholamines, and cortisol) responses to exercise and hypoglycemia combined are synergistically higher than the response to either stimulus alone; 2) exercise-induced increases in insulin action are negated during hypoglycemia by the counterregulatory response; 3) decreased need for exogenous glucose during hypoglycemic compared with euglycemic exercise is due to stimulation of endogenous glucose production, which accounts for approximately 30% of the decrease, and reduction of glucose utilization, which accounts for approximately 70%; and 4) insulin-stimulated nonoxidative glucose metabolism is unaffected by exercise or hypoglycemia, whereas insulin-stimulated oxidative glucose metabolism is selectively increased by exercise and decreased by hypoglycemia. In conclusion, the marked rise in insulin action during exercise is matched, under insulin-induced hypoglycemic conditions, by an equally profound increase in counterregulation. The effectiveness of the potent insulin counterregulatory response may be important in decreasing the magnitude and frequency of exercise-induced hypoglycemia.