Effects of Insulin on Post-Burn Hypermetabolism

胰岛素对烧伤后代谢亢进的影响

• 批准号: 6680125
• 负责人: STEVEN ERIC WOLF
• 金额: $ 32.47万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-02 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6680125
• 关键词: blood flow measurement; body composition; burn therapy; burns; clinical research; drug administration rate /duration; functional ability; glucose clamp technique; hormone therapy; hospital length of stay; human genetic material tag; human subject; hyperinsulinism; insulin; mathematical model; microarray technology; muscle function; outcomes research; photon absorptiometry; polymerase chain reaction; protein biosynthesis; protein metabolism; stable isotope double label; striated muscles; western blottings; wound healing

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.

描述（由申请人提供）： 对损伤的多代谢反应会导致肌肉通过相对于蛋白质合成的蛋白质分解增加而浪费。这种肌肉浪费通过延长愈合并延迟时间恢复，从而增加了发病率和死亡率。我们小组进行的最新研究表明，当在严重燃烧的短期内使用，胰岛素等合成代谢剂会降低蛋白质分解代谢。但是，在整个住院期间，在整个住院治疗人体组成和功能恢复的临床参数上都没有系统地研究。我们研究的目的是表明，胰岛素可以通过胰岛素减弱肌肉浪费，以改善临床结果。在此提案中，我们将研究这些目标：1。确定整个医院过程中尤利克血糖高胰岛素血症对净肌肉蛋白质合成的影响，并将持续的肌肉合成代谢与改善瘦体量和改善严重燃烧的患者的功能恢复相关联。 2。评估胰岛素的生理和分子对骨骼肌的影响，严重燃烧的患者。我们将测试以下假设：a）胰岛素对净蛋白合成的急性影响在整个医院过程中持续存在，b）持续刺激净肌肉蛋白质合成，而整个医院过程中的葡萄糖高胰岛素血症将与可识别的分子变化有关。随着该建议的完成，我们将首次证明与合成代谢剂胰岛素长期治疗不仅会改善生理测量值，而且还将改善瘦体重，肌肉功能和临床结果。我们还将展示发生这些变化的机制，以为与严重损伤相关的分解代谢期间的合成代理疗法提供进一步的基础。