Effects of Insulin on Post-Burn Hypermetabolism

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DESCRIPTION (provided by applicant): The hypermetabolic response to injury causes muscle wasting through increased protein breakdown relative to protein synthesis. This muscle wasting increases morbidity and mortality by prolonging healing and delaying time to full functional recovery. Recent studies done by our group indicate that anabolic agents such as insulin decrease protein catabolism when used over short terms in the severely burned. However, continuous anabolic agent treatment throughout hospitalization on clinical parameters of body composition and functional recovery have not been systematically studied. The goal of our studies is to show that muscle wasting with injury can be attenuated with insulin to improve clinical outcomes. In this proposal, we will investigate these aims: 1. To determine the effect of euglycemic hyperinsulinemia throughout the hospital course on net muscle protein synthesis, and to relate continued muscle anabolism to improved lean body mass and improved functional recovery in severely burned patients. 2. To assess the relationship of insulin's physiologic and molecular effects on skeletal muscle in severely burned patients. We will test the hypotheses that: a) the acute effects of insulin on net protein synthesis are sustained throughout the hospital course, and b) continued stimulation of net muscle protein synthesis with euglycemic hyperinsulinemia throughout the hospital course will be associated with identifiable molecular changes. With completion of this proposal, we will demonstrate, for the first time, that prolonged treatment with the anabolic agent, insulin, will not only result in improved physiologic measurements, but will also improve lean body mass, muscular function, and clinical outcomes. We will also demonstrate mechanisms by which these changes take place, to provide further basis for anabolic agent therapy during catabolism associated with severe injury.