INTRAMUSCULAR TRIGLYCERIDE IN IMPAIRED GLUCOSE TOLERANCE

肌内注射甘油三酯治疗葡萄糖耐量受损

• 批准号: 7719487
• 负责人: LEIGH PERREAULT
• 金额: $ 0.59万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7719487
• 关键词: Acute; Animals; Blood; Characteristics; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Diabetes Mellitus; Exercise; Fibrates; Funding; Gender; Gene Targeting; Grant; Hepatic; Impairment; Institution; Insulin; Insulin Resistance; Intramuscular; Lipolysis; Measures; Methodology; Muscle; Non-Insulin-Dependent Diabetes Mellitus; Peripheral; Peroxisome Proliferator-Activated Receptors; Prevention; Randomized; Research; Research Personnel; Resources; Role; Site; Skeletal Muscle; Source; Tissue Sample; Tissues; Training Programs; Triglycerides; United States National Institutes of Health; Week; Woman; glucose output; glucose uptake; impaired glucose tolerance; insulin sensitivity; interest; men; stable isotope

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Insulin resistance, defined as an impairment in insulin's ability to stimulate peripheral glucose uptake, as well as suppress hepatic glucose output and lipolysis, are major characteristics of impaired glucose tolerance (IGT) and type 2 diabetes. The mechanisms by which insulin resistance develops are unclear. Skeletal muscle is the major tissue responsible for insulin action on peripheral glucose uptake, and therefore has been implicated as a primary site for the development of insulin resistance. Intramuscular triglyceride (IMTG) content and turnover, specifically, have been the topics of considerable recent interest as the amount of IMTG correlates strongly with insulin sensitivity. Substantial data exists that healthy men and women may use IMTG differently, especially during exercise. We speculate that this gender-dependent mechanism for IMTG use is lost in the development of IGT. Our first aim will describe IMTG content and turnover at baseline and during acute exercise in men and women with IGT. The second and third aims of the study will attempt to explain the mechanisms by which men and women lose the ability to turnover IMTG once they develop IGT. We hypothesize that women rely on oxidative capacity of muscle, whereas men rely on the activation of PPAR target genes, as these have been shown in animal studies. To differentiate these mechanisms, men and women with IGT will be randomized to either an exercise training program (to increase oxidative capacity) or fibrate therapy (to activate PPAR for 12 weeks. Will we combine blood and tissue sampling, stable isotope methodology, and measures of insulin sensitivity in pursuit of these aims? Better understanding the role of IMTG content and turnover in the development of insulin resistance in men and women may guide our therapy in the prevention and treatment of diabetes.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 胰岛素抵抗，被定义为胰岛素刺激外周葡萄糖摄取能力的损害，以及抑制肝葡萄糖输出和脂解，是葡萄糖耐受性受损（IGT）和2型糖尿病的主要特征。 胰岛素耐药性产生的机制尚不清楚。 骨骼肌是负责胰岛素作用对周围葡萄糖摄取的主要组织，因此已被视为发展胰岛素抵抗的主要部位。 肌肉内甘油三酸酯（IMTG）含量和周转率，特别是最近引起了近期兴趣的主题，因为IMTG的量与胰岛素敏感性密切相关。 存在大量数据表明，健康的男人和女性可能以不同的方式使用IMTG，尤其是在运动过程中。 我们推测，这种用于IMTG使用的性别依赖性机制在IGT的发展中丢失了。 我们的第一个目的将描述IMTG的内容和基线的流失，以及在患有IGT的男性和女性的急性运动中。 该研究的第二和第三目标将试图解释男人和女人一旦开发IGT的能力而失去流失的能力的机制。 我们假设女性依赖肌肉的氧化能力，而男性则依赖于PPAR靶基因的激活，因为这些靶基因已在动物研究中显示。 To differentiate these mechanisms, men and women with IGT will be randomized to either an exercise training program (to increase oxidative capacity) or fibrate therapy (to activate PPAR for 12 weeks. Will we combine blood and tissue sampling, stable isotope methodology, and measures of insulin sensitivity in pursuit of these aims? Better understanding the role of IMTG content and turnover in the development of insulin resistance in men and women may guide our therapy in糖尿病的预防和治疗。