INSULIN RESISTANCE AND PROTEIN METABOLISM

胰岛素抵抗和蛋白质代谢

• 批准号: 6790873
• 负责人: WIlliam J Evans
• 金额: $ 26.81万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6790873
• 关键词: dietary control; glucose tolerance; glucose tolerance test; human old age (65+); human subject; insulin sensitivity /resistance; metformin; muscle metabolism; muscle proteins; patient oriented research; protein biosynthesis; restricted physical activity

Aging is associated with decreased skeletal muscle mass and increased total body and visceral fat. Elderly people are the most likely segment of the population to remain in bed for extended periods of time for a variety of reasons. Considerable literature exists on the effects of prolonged bedrest in healthy young people---accelerated loss of muscle and the development of insulin resistance--but very little is known about the physiological, metabolic, and functional consequences of bedrest in older people. Therefore, the effects of 10 days of bedrest will be examined in two groups of elderly men and women: normal glucose tolerance (NGT) and impaired glucose tolerance (IGT). The overall goal is to examine the effects of reduced insulin action on skeletal muscle protein metabolism. Five hypotheses will be tested. (1) Insulin resistance exerts an important effect on muscle protein metabolism. (2) Hepatic insulin resistance plays a role in the bedrest-induced peripheral insulin resistance with IGT, Increased hepatic glucose production, even during conditions of elevated insulin levels will result in hyperglycemia and reduced muscle fat oxidation. It is clear that bedrest increases tissue sensitivity to cortisol, potentially exacerbating the hepatic insulin resistance and accelerating loss of muscle protein. (3) Reduced insulin-stimulated glucose disposal results in a decreased rate of muscle protein synthesis and an accelerated loss of muscle during bedrest. Specifically, individuals with NGT will demonstrate reduced loss of muscle compared with those individuals with IGT. (4) Insulin resistance and bedrest will result in an alteration in the skeletal muscle insulin signaling cascade ultimately affecting the rate of muscle protein synthesis. (5) Metformin, a powerful hypoglycemic agent, will prevent many of the bedrest induced adaptations in subjects with IGT. Dietary intake during bedrest will be carefully controlled (eucaloric with 0.8 g protein ? kg-1 ? d-1) so that nitrogen balance may be measured during the entire 10-day period. This project and the interaction with the other projects in this PPG will, for the first time, examine the effect of bedrest in elderly people and provide critical information for the clinical management of bedrest-induced metabolic abnormalities in this vulnerable population.

衰老与骨骼肌质量减少以及总体和内脏脂肪的增加有关。 由于各种原因，老年人是最有可能长时间躺在床上的人群。关于健康年轻人的长时间床上的影响，存在大量文献 - 加速肌肉的丧失和胰岛素抵抗的发展 - 但对老年人的生理，代谢和功能后果知之甚少。因此，将在两组老年男性和女性中检查10天的卧床：正常的葡萄糖耐受性（NGT）和葡萄糖耐受性受损（IGT）。总体目标是检查胰岛素作用减少对骨骼肌蛋白质代谢的影响。将检验五个假设。 （1）胰岛素抵抗对肌肉蛋白质代谢产生重要影响。 （2）肝胰岛素抵抗起作用 在床质引起的IGT耐药性胰岛素抵抗中，即使在胰岛素水平升高的情况下，肝葡萄糖的产生也会增加，也会导致高血糖症和肌肉脂肪氧化减少。显然，床上架增加了组织对皮质醇的敏感性，可能加剧肝胰岛素抵抗和加速肌肉蛋白的丧失。 （3）减少胰岛素刺激的葡萄糖处置导致肌肉蛋白合成率降低，并且在卧床期间加速了肌肉的损失。具体而言，与患有IGT的人相比，NGT的个体将表现出肌肉损失的减少。 （4）胰岛素抵抗和卧床将导致骨骼肌胰岛素信号传导级联反应最终影响肌肉蛋白质合成的速率。 （5）二甲双胍是一种强大的降血糖剂，​​将防止IGT受试者的许多床架诱导的适应性。将仔细控制床上的饮食摄入量（用0.8 g蛋白？kg-1？d-1），以便在整个10天期间都可以测量氮平衡。这个项目和 与该PPG中其他项目的互动将首次检查床上对老年人的影响，并为这种脆弱人群的床上诱导的代谢异常提供关键信息。