Mechanisms by which strength training ameliorates the Metabolic Syndrome

力量训练改善代谢综合症的机制

• 批准号: 8006750
• 负责人: CHARLES A STUART
• 金额: $ 0.67万
• 依托单位: EAST TENNESSEE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-20 至 2010-04-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8006750
• 关键词: 5' -AMP-activated protein kinase; Adult; Aerobic; Affect; Anatomy; Back; Behavior Therapy; Bicycling; Biochemical; Biogenesis; Blood Glucose; Blood flow; Body Composition; Central obesity; Clinical; Clinical Research; Coronary heart disease; Data; Development; Diabetes Mellitus; Diagnosis; Electron Transport; Elements; Enzymes; Epidemic; Euglycemic Clamping; Evaluation; Excess Mortality; Exercise; Fatty acid glycerol esters; Fiber; Gene Targeting; Genes; Glucose; Glucose Clamp; Glucose Transporter; Goals; Hexose Transporter; Human; Hyperglycemia; Hyperinsulinism; Hyperlipidemia; Hypertension; Hypertrophy; Immunoblotting; Insulin; Insulin Resistance; Intramuscular; Knowledge; Lead; Life Expectancy; Life Style; Link; Measures; Metabolic syndrome; Mitochondria; Mitochondrial DNA; Molecular; Muscle; Muscle Cells; Muscle Contraction; Muscle Fibers; Needle biopsy procedure; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Overweight; Oxygen; PTGS1 gene; Pathway interactions; Peroxisome Proliferator-Activated Receptors; Persons; Pharmaceutical Preparations; Pilot Projects; Prediabetes syndrome; Prevalence; Prevention; Protein Biosynthesis; Protein Isoforms; Protein Kinase; Recruitment Activity; Regulator Genes; Regulatory Pathway; Research; Research Personnel; Resistance; Risk; Secure; Sirolimus; Study Subject; Subcellular Fractions; System; Techniques; Testing; Thigh structure; Time; Tobacco use; Training; United States; White Fiber; White Muscle Fibers; blood glucose regulation; cytochrome c; diabetes prevention program; experience; fasting plasma glucose; glucose uptake; high risk; improved; insulin sensitivity; mTOR protein; novel; programs; protein metabolism; public health relevance; sedentary; strength training; tool; treatment strategy; uptake; vastus lateralis

DESCRIPTION (provided by applicant): Life style alterations can be powerful deterrents to developing type 2 diabetes and are cornerstones of the treatment of this condition. Both aerobic and resistance exercise improve diabetes blood glucose control and insulin resistance. These two types of exercise appear to exert their effects on different muscle fiber types - red for endurance and white for strength. Similar to the effects of endurance exercise training, strength training increases muscle glucose transporter isoform 4 (GLUT4), but in contrast, mitochondria numbers do not increase. We hypothesize (1) that strength training in persons with pre-diabetes may be effective in reversing insulin resistance by novel mechanisms that are distinct from the endurance training-induced mitochondrial biogenesis. We further hypothesize (2) that resistance exercise training enhances whole body insulin action primarily by increasing the white fiber size via the protein kinase mammalian target of rapamycin (mTOR) and improves insulin-stimulated glucose uptake by increased GLUT4 expression primarily in white fibers of the trained muscles. In this application, we will perform eight weeks of progressive strength training on ten subjects with the Metabolic Syndrome who are at high risk for developing type 2 diabetes and on ten sedentary control subjects. This project builds on our experience with a study of focused resistance training whose results are presented in this application. In this pilot study, subjects exercised on stationary bicycles for six weeks causing muscle GLUT4 and phopho-mTOR to increase substantially, but maximal oxygen uptake (VO2max), phospho-AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-3 co-activator (PGC-11), and mitochondrial markers did not change. Our hypotheses will be tested by two Specific Aims. (1) Subjects at high risk for diabetes will undergo progressively increasing intensity resistance exercise training and increased strength and improved insulin responsiveness will both be quantified to demonstrate significant benefit, and (2) quantify the effect of resistance exercise training on anatomic and functional adaptation in muscle. We will characterize fiber type, fiber size, fiber-specific changes in mitochondrial DNA and enzymes, fiber-specific changes in the principle glucose transporters in muscle (GLUT4, GLUT5, and GLUT12), and evaluate changes in two distinct intramuscular pathways (AMPK, mTOR) and regulatory factors (PGC-11, PPAR3, PPAR4) using immunoblots of muscle subcellular fractions and immunohistochemical techniques. These evaluations of molecular mechanisms will also include assessing changes in full human Affymetrix gene array data that may move us to new potential resistance training-regulated gene targets. It is the long-term goal of this team of investigators to understand the interplay between life style changes and pharmacological agents in the prevention and treatment of diabetes. Our results will facilitate the development of more effective clinical options to turn back the epidemic of obesity and diabetes in the United States. PUBLIC HEALTH RELEVANCE: Prevention and treatment strategies for diabetes use exercise as the cornerstone. Even though endurance training and strength training both improve insulin resistance, strength training may be better suited for persons at risk for type 2 diabetes. We will expand our pilot studies of muscle adaptation induced by resistance exercise training to determine the biochemical mechanisms that will cause people with the Metabolic Syndrome to secure major benefit from intense strength training.

描述（由申请人提供）：生活方式的改变可能是发展2型糖尿病的有力威慑，是治疗这种病的基石。有氧运动和耐药性运动都可以改善糖尿病的血糖控制和胰岛素抵抗。这两种运动似乎对不同的肌肉纤维类型产生了影响 - 红色耐力，而白色则具有强度。与耐力运动训练的影响相似，力量训练会增加肌肉葡萄糖转运蛋白同工型4（GLUT4），但相反，线粒体数不会增加。我们假设（1）在糖尿病前患者中的力量训练可能有效地通过与耐力训练引起的线粒体生物发生不同的新机制逆转胰岛素抵抗。我们进一步假设（2），耐药运动训练主要通过通过蛋白激酶哺乳动物型雷帕霉素（MTOR）靶标增加白色纤维大小来增强全身胰岛素作用，并改善胰岛素刺激的葡萄糖摄取，主要通过在训练有素肌肉的白色纤维中增加GLUT4表达增加的GLUT4表达。在此应用中，我们将对具有代谢综合征的十个受试者进行八周的渐进式力量训练，他们患有2型糖尿病和十名久坐控制受试者的高风险。该项目以我们对集中抵抗训练的研究为基础，该项目在本应用程序中呈现了结果。在这项试点研究中，在固定自行车上进行六周的受试者，导致肌肉glut4和phopho-mtor大幅增加，但最大的氧气吸收（VO2MAX），磷酸化AMP激活的蛋白激酶激酶（AMPK），过氧化物剂增殖物激活的受体-3 co-3 co-1 coirath（PCCIARTIROTH）（pcirotch and Markoust dientr and M.M. M. Mindrort and M.M. M.M.我们的假设将通过两个具体目标来检验。 （1）糖尿病高风险的受试者将逐渐增加强度耐药性运动训练，并提高强度和提高的胰岛素反应能力，都可以量化以证明巨大的益处，（2）量化耐药性运动训练对肌肉中解剖学和功能适应的影响。 We will characterize fiber type, fiber size, fiber-specific changes in mitochondrial DNA and enzymes, fiber-specific changes in the principle glucose transporters in muscle (GLUT4, GLUT5, and GLUT12), and evaluate changes in two distinct intramuscular pathways (AMPK, mTOR) and regulatory factors (PGC-11, PPAR3, PPAR4) using immunoblots of肌肉亚细胞分数和免疫组织化学技术。分子机制的这些评估还将包括评估全人类Affymetrix基因阵列数据的变化，这些变化可能会使我们进入新的潜在抗性训练受训练受调节的基因靶标。这支研究人员的长期目标是了解生活方式变化与药理学剂之间的相互作用在预防和治疗糖尿病方面的相互作用。我们的结果将促进更有效的临床选择的发展，以撤回美国肥胖和糖尿病的流行。公共卫生相关性：糖尿病的预防和治疗策略使用运动作为基石。即使耐力训练和力量训练都可以提高胰岛素抵抗，但力量训练可能更适合患有2型糖尿病风险的人。我们将扩大对抗药性运动训练引起的肌肉适应性的试点研究，以确定会导致代谢综合征的人的生化机制，从而从强烈的力量训练中获得重大利益。