AGE EFFECTS ON EXERCISE STIMULATION OF GLUCOSE TRANSPORT

年龄对运动刺激葡萄糖转运的影响

• 批准号: 2051279
• 负责人: Gregory D. Cartee
• 金额: $ 8.96万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2051279
• 关键词: aging; caloric dietary content; disease /disorder proneness /risk; electrostimulus; exercise; glucose transport; hyperglycemia; hyperinsulinism; insulin sensitivity /resistance; laboratory rat; muscle contraction; muscle metabolism; nutrition related tag; sarcolemma; scintillation counter; striated muscles; transport proteins; ultracentrifugation

The broad, long-range objectives of this project are to identify the mechanisms for age-related skeletal muscle insulin-resistance, to determine if the defect is primarily insulin-resistance or a reduction in the ability to elevate glucose transport by various stimuli (including exercise), to determine if the age-related defect is inevitable or if old muscle retains the capacity to upregulate glucose transport, and to determine if age modifies the increased insulin sensitivity after exercise. Insulin- and exercise-stimulation will be studied because of their physiological importance in the regulation of muscle glucose metabolism. Fischer 344 rats (12, 18 or 24 mos of age) will be the animal model because they remain lean throughout their lifespan, enabling the effects of age to be studied independent of obesity, which has confounded interpretation of earlier studies. The Specific Aims are to determine the effect of age on 1) the insulin-stimulated increase of glucose transport rate and sarcolemmal glucose transporter content, 2) the capacity of moderate caloric restriction to cause upregulation of glucose transport, 3) the contraction- stimulated increase of glucose transport rate and sarcolemmal glucose transporter content, and 4) the enhanced insulin-stimulated glucose transport rate following contractile activity. The health-relatedness of the project is that advancing age is characterized by an increased prevalence of hyperglycemia and hyperinsulinemia. These conditions are associated with a greater risk for many age-related diseases, including hypertension, cardiovascular and cerebrovascular disease. The cellular mechanisms responsible for the insulin resistance in older individuals are undetermined, but skeletal muscle, quantitatively the major insulin- sensitive tissue, plays a pivotal role. Muscle glucose transport will be studied because it is the rate-limiting step for muscle glucose metabolism and preliminary evidence indicates a defect at this site. The model to be used to study glucose transport rate will be the perfused hindlimb muscle preparation. Electrically stimulated contractile activity will be used as a model for in vivo exercise in order to isolate, as much as possible, age- related changes in the skeletal muscle from changes in other tissues. Moderate caloric restriction, identified by preliminary research as the only intervention known to reverse the insulin-resistance of old muscle, will be used as an experimental probe to determine the mechanism by which old muscle can upregulate its glucose transport system.

该项目的广泛，远程目标是确定 与年龄有关的骨骼肌胰岛素抵抗的机制，以确定 如果缺陷主要是胰岛素抵抗或能力的降低 通过各种刺激（包括运动）提升葡萄糖转运 确定与年龄相关的缺陷是不可避免的还是旧的肌肉保留 上调葡萄糖转运的能力，并确定年龄是否 修饰运动后胰岛素敏感性提高。 胰岛素和 由于其生理学，将研究运动刺激 调节肌肉葡萄糖代谢的重要性。 Fischer 344 大鼠（年龄12、18或24 mos）将是动物模型，因为它们保持 在整个生命周期中倾斜，使年龄的影响能够研究 独立于肥胖，这与早期的解释混淆了 研究。 具体目的是确定年龄对1） 胰岛素刺激的葡萄糖传输速率和肌膜的增加 葡萄糖转运蛋白含量，2）中等热量的能力 限制导致葡萄糖转运上调的限制，3）收缩 - 刺激葡萄糖转运速率和肌膜葡萄糖的增加 转运蛋白含量，4）增强的胰岛素刺激的葡萄糖 收缩活动后的运输速率。 与健康相关的 该项目是进步年龄的特征是增加 高血糖和高胰岛素血症的患病率。 这些条件是 与许多与年龄有关疾病的风险更大，包括 高血压，心血管和脑血管疾病。 细胞 负责老年胰岛素抵抗的机制是 不确定但骨骼肌，定量是主要的胰岛素 敏感的组织起着关键作用。 肌肉葡萄糖的传输将是 研究是因为这是肌肉葡萄糖代谢的限速步骤 初步证据表明该站点存在缺陷。 模型是 用于研究葡萄糖运输速率的灌注后肌 准备。 电刺激的收缩活动将被用作 一个体内运动的模型，以尽可能分离年龄 其他组织变化的骨骼肌相关变​​化。 中等热量限制，由初步研究确定为 只有已知的干预措施来扭转旧肌肉的胰岛素抵抗， 将用作实验探针，以确定 旧肌肉可以上调其葡萄糖运输系统。