EFFECT OF INSULIN AND AMINO ACIDS ON STRESS INDUCED PROTEOLYSIS

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Corticosteriod excess that accompanies major injury or trauma results in an accelerated muscle protein breakdown. The increased proteolysis is especially threatening as it results in muscle wasting and debility. Hypercortisolemia is characterized by an increase in muscle protein breakdown, while protein synthesis decreases or remains unchanged. Evidence in animal models and indirect human data suggest that muscle amino acid uptake is impaired. Therefore, we will investigate the hypothesis protein breakdown is central in mediating changes in muscle protein metabolism. We will determine the effect of acute (8hr) and four days of cortisol treatment (6 mg/m2/hr) on transmembrane amino acid transport. We will subsequently determine the effect of anabolic factors (insulin and amino acid) on amino acid transport and muscle protein metabolism during cortisol excess. Stable isotope tracers will be utilized to measure these effects in normal volunteers.