Exercise Training in Insulin Resistant Non-Diabetics

胰岛素抵抗非糖尿病患者的运动训练

• 批准号: 6729959
• 负责人: IRA D. GOLDFINE
• 金额: $ 33.67万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6729959
• 关键词: adipocytes; biological signal transduction; body composition; cardiovascular disorder risk; clinical research; computed axial tomography; diabetes risk; disease /disorder prevention /control; exercise; glucose clamp technique; glucose metabolism; glucose tolerance; human subject; insulin receptor; insulin sensitivity /resistance; metabolic syndrome; photon absorptiometry; striated muscles

DESCRIPTION (provided by applicant): The purpose of this proposal is to investigate the effects of exercise training in lean, non diabetic individuals who have insulin resistance, but normal glucose tolerance. Insulin resistance is a major feature of most patients with type 2 diabetes mellitus (T2D). It is not appreciated, however, that insulin resistance of a similar nature and magnitude also occurs in up to 25% of lean, non-diabetic individuals with normal glucose tolerance. In this group, insulin resistance, in the absence of hyperglycemia, predisposes them to: 1) T2D; 2) the Metabolic Syndrome X (hypertension, dyslipidemia, and coronary artery disease); and 3) cancer. However, in these non diabetics, intervention strategies have not been developed, and the biochemical mechanisms of insulin resistance have not been extensively studied. For two major reasons therefore we propose to investigate this insulin resistant group. First, because they are at a higher risk for clinical disease than insulin sensitive subjects, it is important to clearly document that exercise is a beneficial intervention for them. Second, in this group, an analysis of their insulin resistance is not confounded (as in the usual T2D patient) by metabolic abnormalities resulting from obesity or hyperglycemia. Therefore, in these subjects, we plan to measure whole body insulin sensitivity by insulin clamp, and the major components of the insulin signaling system in muscle both before and after exercise training. The components to be studied are: the insulin receptor; IRS proteins; PI 3-kinase; PKB/AKT; and GLUT 4. In addition, we will study the major known regulators of the system: adiponectin; PTP 1B; PC-l; IKK; NF-KB; and PKC. Next these resistant individuals will undergo 14 weeks of exercise training to increase insulin sensitivity. After training they will be restudied and the results obtained compared to two control groups: non-exercised, insulin resistant subjects; and insulin sensitive subjects. We believe that these studies will: 1) document the beneficial improvements insulin sensitivity that occur with exercise training in insulin resistant, non diabetic subjects; 2) further our understanding of the biochemical defects that underlie insulin resistance; and 3) have the potential to reveal new cellular targets for therapeutic intervention.

描述（由申请人提供）：该提案的目的是研究具有胰岛素抵抗但正常葡萄糖耐受性的非糖尿病患者运动训练的影响。胰岛素抵抗是大多数2型糖尿病（T2D）患者的主要特征。然而，不理解，相似性质和幅度的胰岛素抵抗也发生在多达25％的瘦糖尿病患者中，具有正常的葡萄糖耐受性。 在这一组中，胰岛素抵抗，在没有高血糖的情况下，使它们容易受到：1）T2D； 2）代谢综合征X（高血压，血脂异常和冠状动脉疾病）； 3）癌症。 但是，在这些非糖尿病患者中，尚未开发干预策略，并且尚未对胰岛素抵抗的生化机制进行广泛的研究。 因此，由于两个主要原因，我们建议研究这种胰岛素耐药组。 首先，由于与胰岛素敏感受试者的临床疾病风险更高，因此清楚地记录运动对他们是有益的干预非常重要。 其次，在这一组中，对它们的胰岛素抵抗的分析并没有被肥胖或高血糖引起的代谢异常混淆（如通常的T2D患者中）。 因此，在这些受试者中，我们计划通过胰岛素夹来衡量全身胰岛素敏感性，以及运动训练前后肌肉中胰岛素信号系统的主要成分。 要研究的成分是：胰岛素受体； IRS蛋白质； Pi 3-激酶； pkb/akt;和Glut 4。此外，我们将研究系统的主要调节剂：脂联素； PTP 1B; PC-L; ikk; NF-KB;和PKC。 接下来，这些抵抗力的人将接受14周的运动训练，以提高胰岛素敏感性。 训练后，它们将被重新降低，并获得了与两个对照组相比获得的结果：未受过胰岛素的受试者；和胰岛素敏感受试者。 我们认为，这些研究将：1）记录在抗胰岛素，非糖尿病患者中运动训练时发生的有益改善胰岛素敏感性； 2）进一步了解胰岛素抵抗的生化缺陷； 3）有可能揭示用于治疗干预的新细胞靶标。