Abstract
Previous studies in man and pancreatectomized dogs have indicated that alterations of the pharmacokinetics of subcutaneously injected insulin during physical activity may contribute to exercise-induced hypoglycaemia in insulin-treated diabetic patients. We have directly measured the appearance of subcutaneously injected insulin in the circulation and assessed its distribution to different tissues using a recently developed semisynthetic homogeneous [3H]insulin as a tracer. Following subcutaneous injection in rats of [3H]insulin in amounts insufficient to exert significant biological activity in intact animals, circulating levels of exogenous insulin were measured as plasma radioactivity co-migrating with insulin during gel filtration chromatography. Strenuous treadmill running accelerated the mobilization of subcutaneously injected [3H] insulin and resulted in a significant elevation of circulating levels of exogenous insulin early during exercise, followed by decreased levels in the post-exercise period. In addition, exercise induced a redistribution of 3H radioactivity in tissues, mainly increasing that found in skeletal muscle. This direct demonstration of altered pharmacokinetics of subcutaneously injected insulin during exercise provides, at least in part, a mechanism for the exercise-induced hypoglycemia seen following insulin injections in animals and during insulin treatment in man.
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