INSULIN RESISTANCE AND PROTEIN METABOLISM

衰老与骨骼肌量减少、全身和内脏脂肪增加有关。 老年人是最有可能因各种原因长时间卧床的人群。有相当多的文献研究了长时间卧床休息对健康年轻人的影响-肌肉加速丧失和胰岛素抵抗的发展--但对老年人卧床休息的生理、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测10天卧床休息的效果：正常糖耐量(NGT)和糖耐量受损(IGT)。总体目标是检查胰岛素作用减弱对骨骼肌蛋白质代谢的影响。五个假设将被检验。(1)胰岛素抵抗对肌肉蛋白质代谢有重要影响。(2)肝脏胰岛素抵抗起一定作用 在卧床诱导的外周胰岛素抵抗合并IGT的患者中，肝脏葡萄糖生成增加，即使在胰岛素水平升高的情况下也会导致高血糖和肌肉脂肪氧化减少。很明显，卧床休息增加了组织对皮质醇的敏感性，潜在地加剧了肝脏的胰岛素抵抗，并加速了肌肉蛋白质的损失。(3)减少胰岛素刺激的葡萄糖处理会导致卧床期间肌肉蛋白质合成速率降低和肌肉加速丧失。具体地说，与IGT患者相比，NGT患者的肌肉损失会减少。(4)胰岛素抵抗和卧床休息会导致骨骼肌胰岛素信号转导通路的改变，最终影响肌肉蛋白质合成的速度。(5)降糖剂二甲双胍可阻止IGT受试者卧床时的许多适应。卧床期间的饮食摄入量将被仔细控制(含0.8克蛋白质的优卡？Kg-1？D-1)，以便可以在整个10天期间测量氮平衡。这个项目和 与PPG中的其他项目的互动将首次检查卧床休息对老年人的影响，并为这一脆弱人群卧床休息引起的代谢异常的临床管理提供关键信息。

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.