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: 6863622
• 负责人: IRA D. GOLDFINE
• 金额: $ 33.72万
• 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/6863622
• 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）：本提案的目的是研究运动训练对具有胰岛素抵抗但葡萄糖耐量正常的非糖尿病瘦个体的影响。胰岛素抵抗是大多数2型糖尿病（T2 D）患者的主要特征。然而，没有意识到，类似性质和程度的胰岛素抵抗也发生在高达25%的具有正常葡萄糖耐量的瘦的非糖尿病个体中。 在该组中，在没有高血糖的情况下，胰岛素抵抗使他们易患：1）T2 D; 2）代谢综合征X（高血压、血脂异常和冠状动脉疾病）;和3）癌症。 然而，在这些非糖尿病患者中，干预策略尚未开发，胰岛素抵抗的生化机制尚未得到广泛研究。 因此，出于两个主要原因，我们建议研究这个胰岛素抵抗组。 首先，因为他们比胰岛素敏感受试者有更高的临床疾病风险，所以必须明确记录运动对他们是有益的干预。 其次，在该组中，对他们的胰岛素抵抗的分析不受肥胖或高血糖症导致的代谢异常的混淆（如在普通的T2 D患者中）。 因此，在这些受试者中，我们计划通过胰岛素钳夹测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; PI 3-激酶; PKB/AKT;和GLUT 4。 此外，我们将研究该系统的主要已知调节因子：脂联素、PTP 1B、PC-1、IKK、NF-κ B和PKC。 接下来，这些抵抗者将接受14周的运动训练，以增加胰岛素敏感性。 训练后，他们将被重新研究，并将获得的结果与两个对照组进行比较：非运动的胰岛素抵抗受试者;和胰岛素敏感受试者。 我们相信，这些研究将：1）记录胰岛素抵抗，非糖尿病受试者的运动训练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）有可能揭示新的治疗干预的细胞靶点。