Interaction of exercise, insulin and hypoglycemia studied using hyperinsulinemic euglycemic and hypoglycemic clamp techniques. Zinker, Bradley A., Robert G. Allison, D. Brooks Lacy, and David H. Wasserman. Department of Molecular Physiology and Biophysics, Vanderbilt University, School of Medicine, Nashville, TN 37232
APStracts 3:0258E, 1996.
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 >17 days prior to study. Following 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 to 150 min) period or an equivalent duration sedentary period. Insulin was infused at 1 mU/kg x min from t=0 to 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 (65 mg/dl) during the insulin infusion. Arteriovenous difference and isotopic (3-3H -glucose, U-14C-glucose) techniques were used to assess glucose metabolism. Insulin levels were 40 [mu]U/ml in all groups. Data show that, (a) counterregulatory hormone (glucagon, catecholamines and cortisol) responses to exercise and hypoglycemia combined are synergistically higher than the response to either stimulus alone; (b) exercise-induced increases in insulin action are negated during hypoglycemia by the counterregulatory response; (c) decreased need for exogenous glucose during hypoglycemic compared to euglycemic exercise is due to stimulation of endogenous glucose production, which accounts for 30% of the decrease, and reduction of glucose utilization which accounts for 70%; and (d) insulin-stimulated non -oxidative glucose metabolism is unaffected by exercise or hypoglycemia, while 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.

Received 20 September 1996; accepted in final form 5 December
1996.
APS Manuscript Number E475-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996