Effects of Insulin on Post-Burn Hypermetabolism

描述（由申请人提供）： 对损伤的高代谢反应通过相对于蛋白质合成增加的蛋白质分解引起肌肉消耗。这种肌肉消耗通过延长愈合和延迟完全功能恢复的时间而增加发病率和死亡率。我们小组最近的研究表明，在严重烧伤患者中，短期使用合成代谢药物如胰岛素可降低蛋白质催化剂。然而，在整个住院期间持续合成代谢药物治疗对身体组成和功能恢复的临床参数的影响尚未得到系统研究。我们研究的目的是表明，损伤性肌肉萎缩可以用胰岛素减轻，以改善临床结果。在本建议中，我们将调查这些目标：1。确定在严重烧伤患者住院期间血糖正常的高胰岛素血症对净肌肉蛋白合成的影响，并将持续的肌肉抑制与改善瘦体重和改善功能恢复联系起来。2.探讨胰岛素对严重烧伤患者骨骼肌的生理效应与分子效应的关系。我们将检验以下假设：a）胰岛素对净蛋白质合成的急性效应在整个住院过程中持续存在，和B）在整个住院过程中，血糖正常的高胰岛素血症持续刺激净肌肉蛋白质合成将与可识别的分子变化相关。随着这项提案的完成，我们将首次证明，长期使用合成代谢药物胰岛素治疗不仅会改善生理测量，而且还会改善瘦体重，肌肉功能和临床结果。我们还将展示这些变化发生的机制，为严重损伤相关的catabolism期间的合成代谢药物治疗提供进一步的依据。

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.