Effects of Insulin on Post-Burn Hypermetabolism

胰岛素对烧伤后代谢亢进的影响

• 批准号: 7116295
• 负责人: STEVEN ERIC WOLF
• 金额: $ 26.14万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 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 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7116295
• 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）： 对损伤的代谢亢进反应通过相对于蛋白质合成增加的蛋白质分解导致肌肉萎缩。这种肌肉消耗会延长愈合时间并延迟完全功能恢复的时间，从而增加发病率和死亡率。我们小组最近进行的研究表明，在严重烧伤患者中短期使用胰岛素等合成代谢药物会减少蛋白质分解代谢。然而，住院期间持续合成代谢药物治疗对身体成分和功能恢复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胰岛素可以减轻损伤引起的肌肉萎缩，从而改善临床结果。在本提案中，我们将研究以下目标： 1. 确定整个住院过程中血糖正常的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严重烧伤患者的去脂体重改善和功能恢复改善联系起来。 2. 评估胰岛素对严重烧伤患者骨骼肌的生理和分子影响的关系。我们将测试以下假设：a）胰岛素对净蛋白质合成的急性影响在整个住院过程中持续存在，b）在整个住院过程中用正常血糖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，长期使用合成代谢剂胰岛素治疗不仅会改善生理测量，而且还会改善去脂体重、肌肉功能和临床结果。我们还将展示这些变化发生的机制，为与严重损伤相关的分解代谢期间的合成代谢药物治疗提供进一步的基础。