Considerable information is available regarding the effects of endurance training on the insulin sensitivity of carbohydrate metabolism in skeletal muscles of diabetic and normal animals. Little is known, however, regarding alterations in sensitivity of protein metabolism. The adaptation of skeletal muscle to endurance training involves alterations in protein metabolism which lead to increases in the concentration of specific proteins. In contrast, contractile activity against a load results in alterations in protein metabolism that lead to hypertrophy. The protein metabolic responses to the two types of activity occur in insulin-deficient diabetic rats as well as normal rats. We propose to determine the influence of muscle activity on the insulin sensitivity of both muscle protein and carbohydrate metabolism in vitro in the fast twitch soleus and slow twitch epitrochlearis and extensor digitorum longus muscles isolated from normal and diabetic rats. In parallel experiments, the sensitivity of protein synthesis in vivo in fast and slow twitch skeletal muscles of sedentary and endurance trained diabetic rats to stimulation by insulin infusion will be determined. Finally, we will test in in vitro experiments the hypothesis that glucocorticoids are important factors in controlling the insulin sensitivity of protein metabolism in skeletal muscles. These studies will provide important new information on the adaptive response of skeletal muscle to endurance exercise and contractile activity and will provide insight into the mechanism by which physical conditioning improves the function of muscle and alters the sensitivity of the organism to the anabolic influence of insulin.
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