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: 7214521
• 负责人: Joseph A Houmard
• 金额: $ 0.26万
• 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 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7214521
• 关键词: Age; related; insulin; resistance; muscle

DESCRIPTION (provided by applicant): Advancing age is typically accompanied by insulin resistance. Relatively little, however, is known concerning the cellular mechanism(s) responsible for age-related insulin resistance, particularly 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 subsequently contributes to insulin resistance. Our working hypothesis is that insulin signal transduction is reduced in aged skeletal muscle due to inhibition from increased muscle lipid content and/or 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 enhanced 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/or impaired oxidative capacity contribute to the decrement. Specific Aim 2: Determine if lipid accumulation and or reduced muscle oxidative capacity impairs insulin signal transduction in human skeletal muscle. Using a primary human skeletal muscle cell culture system we will determine if lipid exposure impairs insulin signaling and if decrements in lipid oxidation (akin to aging) induce insulin resistance. With PPARa agonist treatment we will conversely increase muscle oxidative capacity in muscle cells and in aged individuals and determine if this increase reverses lipid-induced insulin resistance. Specific Aim 3: 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 changes in muscle lipid content and/or oxidative capacity are mechanisms that can explain such changes.

描述（由申请人提供）：年龄增长通常伴随着胰岛素抵抗。然而，关于与年龄相关的胰岛素抵抗的细胞机制，特别是在胰岛素作用的主要靶组织骨骼肌中，所知相对较少。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的衰老过程而受损，这随后导致胰岛素抵抗。我们的工作假设是，由于肌肉脂质含量增加和/或氧化能力降低的抑制，老年骨骼肌中的胰岛素信号转导减少。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：确定胰岛素信号转导是否随着人骨骼肌的衰老而受损。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/或氧化能力受损是否有助于减少。具体目标二：确定脂质蓄积和/或肌肉氧化能力降低是否会损害人骨骼肌中的胰岛素信号转导。使用原代人骨骼肌细胞培养系统，我们将确定脂质暴露是否会损害胰岛素信号传导，以及脂质氧化（类似于衰老）的减少是否会诱导胰岛素抵抗。通过PPARa激动剂治疗，我们将相反地增加肌肉细胞和老年个体中的肌肉氧化能力，并确定这种增加是否逆转脂质诱导的胰岛素抵抗。具体目标3：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运动训练中的胰岛素作用，以及肌肉脂质含量和/或氧化能力的变化是否是可以解释这种变化的机制。