Age-related insulin resistance, muscle, and exercise

年龄相关的胰岛素抵抗、肌肉和运动

• 批准号: 7627945
• 负责人: Joseph A Houmard
• 金额: $ 26.72万
• 依托单位: EAST CAROLINA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7627945
• 关键词: 1-Phosphatidylinositol 3-Kinase; Accounting; Affect; Age; Aging; Aging-Related Process; Cardiovascular Diseases; Cell Culture System; Data; Elderly; Exercise; Funding; GLUT4 gene; Genes; Glucose Transporter; Hand; Human; Hypertension; Individual; Insulin; Insulin Resistance; Lipids; Mediating; Muscle; Muscle Fibers; Non-Insulin-Dependent Diabetes Mellitus; Physical activity; Precipitating Factors; Public Health; Research Personnel; Resistance; Signal Pathway; Signal Transduction; Skeletal Muscle; Small Interfering RNA; Testing; Tissues; Training; United States; Work; age related; aged; etomoxir; glucose transport; improved; insulin signaling; muscle aging; overexpression; oxidation; programs; strength training

DESCRIPTION (provided by applicant): Advancing age is often accompanied by insulin resistance. Relatively little, however, is known concerning the cellular mechanism(s) responsible for age-related insulin resistance in the primary target tissue for insulin action, skeletal muscle. In the current proposal, the hypothesis to be tested is that the insulin signal leading to glucose transport is impaired with the aging process in human skeletal muscle, which induces insulin resistance. Our working hypothesis is that insulin signal transduction is impaired in aged skeletal muscle due to inhibition from increased muscle lipid content and reduced oxidative capacity. As decrements during the aging process can be a consequence of physical inactivity, our secondary hypothesis is that age-related insulin resistance is compensated for with exercise training by enhancing insulin signaling. The following aims will test these hypotheses. Specific Aim 1. Determine if insulin signal transduction is impaired with aging in human skeletal muscle. We will examine if insulin signal transduction in skeletal muscle is impaired with the aging process in humans and if muscle lipid accumulation and reduced oxidative capacity contribute to the decrement. Specific Aim 2. Determine the cellular mechanism(s) by which insulin action is enhanced with physical activity in aged skeletal muscle. We will determine if enhanced insulin signal transduction contributes to the improvement in insulin action seen with endurance- and resistance-oriented exercise training in aged individuals and if a reduction in bioactive muscle lipid content is the unifying mechanism by which physical activity enhances insulin action in the aged, regardless of exercise mode. Specific Aim 3. Determine if muscle oxidative capacity specifically influences insulin signal transduction in human skeletal muscle. With aging there is a decline in muscle oxidative capacity, which can be at least partially compensated for by endurance-oriented physical activity. By using a primary human cell culture system we intend to determine if oxidative capacity directly influences insulin signaling/insulin action.

描述（申请人提供）：年龄的增长往往伴随着胰岛素抵抗。然而，对于胰岛素作用的主要靶组织骨骼肌中与年龄相关的胰岛素抵抗的细胞机制知之甚少。在目前的提议中，要测试的假设是，导致葡萄糖转运的胰岛素信号随着人类骨骼肌中的老化过程而受损，这诱导胰岛素抵抗。我们的工作假设是，胰岛素信号转导受损，在老年骨骼肌由于抑制从增加肌肉脂质含量和降低氧化能力。由于衰老过程中的胰岛素水平下降可能是身体活动不足的结果，我们的次要假设是，与年龄相关的胰岛素抵抗通过增强胰岛素信号传导的运动训练得到补偿。以下目标将检验这些假设。 具体目标1.确定人骨骼肌中胰岛素信号转导是否随衰老而受损。我们将研究骨骼肌中的胰岛素信号转导是否随着人类的衰老过程而受损，以及肌肉脂质积累和氧化能力降低是否有助于减少。 具体目标2。确定老年骨骼肌中胰岛素作用随体力活动而增强的细胞机制。我们将确定增强的胰岛素信号转导是否有助于改善老年人耐力和阻力导向的运动训练中的胰岛素作用，以及生物活性肌肉脂质含量的减少是否是体力活动增强老年人胰岛素作用的统一机制，无论运动模式如何。 具体目标3。确定肌肉氧化能力是否特异性地影响人骨骼肌中的胰岛素信号转导。随着年龄的增长，肌肉氧化能力下降，这至少可以通过以耐力为导向的体力活动来部分补偿。通过使用原代人细胞培养系统，我们打算确定氧化能力是否直接影响胰岛素信号传导/胰岛素作用。