INSULIN SENSITIVITY AND INTRACELLULAR SIGNALING OF MUSCLE PROTEIN SYNTHESIS IN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 背景：胰岛素抵抗的发展是衰老的一个共同特征。随着年龄的增长，肌肉质量和力量的丧失也是一个越来越普遍的问题。有证据表明，老年肌肉对胰岛素的反应方式与年轻肌肉不同。本研究的目的是确定老年人肌肉组织对胰岛素和阻力运动的反应。 假设：我们假设老年人的胰岛素抵抗会导致肌肉质量的减少。 我们还假设，阻力运动可以改善老年人的肌肉损失。 具体目标和程序(摘要)： 1.探讨胰岛素和耐力运动对老年人肌肉蛋白质合成影响的相关因素。 2.测定肌肉组织对耐力运动、胰岛素及胰岛素与耐力运动联合作用的时程。 这项初步研究的数据将被用于计划一项更大规模的试验，调查胰岛素抵抗与老年人肌肉损失之间的关系。 实验设计(总结)：这项研究将包括年龄在60-85岁之间的正常健康老年人，他们不参加任何形式的阻力运动。在参与研究之前，受试者将接受全面的筛查访问。受试者将被随机选择(例如，通过掷硬币)，以参与三项研究中的一项。研究1将包括一段休息时间，然后将胰岛素注入股动脉6小时。研究2将包括对腿部进行阻力运动锻炼(即四种不同的腿部锻炼)，然后进行8小时的胰岛素输注。研究3将包括与研究2相同的阻力运动锻炼，但随后将进行8小时的休息，不注射胰岛素。 意义(摘要)：确定导致肌肉丧失和衰老的肌肉代谢缺陷的细胞将为开发有效的治疗骨质疏松症的方法提供所需的信息。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: The development of insulin resistance is a common feature of aging. Loss of muscle mass and strength with aging is also an increasingly common problem. There is evidence that elderly muscle does not respond to insulin in the same manner as young muscle. The purpose of this study is to determine the response of muscle tissue to insulin and resistive exercise in the elderly. Hypothesis: We hypothesize that insulin resistance in the elderly contributes to loss of muscle mass. We also hypothesize that resistance exercise improves the loss of muscle in the elderly. Specific Aims and Procedures (summary): 1. To determine the factors associated with changes in muscle protein synthesis in the elderly in response to insulin and resistive exercise. 2. To determine the time course of the response of the muscle tissue to the resistive exercise, insulin and, the combination of insulin and resistive exercise. The data from this pilot study will be used in planning a larger trial investigating the relationship between insulin resistance and muscle loss in the elderly. Experimental Design (summary): This study will include normal healthy elderly between the ages of 60-85 who do not participate in any form of resistive exercise. Subjects will undergo a comprehensive screening visit prior to participating in the study. Subjects will be randomly selected (for example, by the flip of a coin), to participate in one of three studies. Study 1 will involve a period of rest followed by infusion of insulin for 6 hours into a femoral artery. Study 2 will involve a resistance exercise workout of the legs (i.e. four different leg exercises), followed by an 8-hour insulin infusion period. Study 3 will involve the same resistance exercise workout as Study 2 but will be followed by 8 hours of rest with no insulin infusion. Significance (summary): Identification of the cells responsible for defects in muscle metabolism that lead to muscle loss and aging will provide the information needed for development of effective therapies to treat sarcopenia.