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: 7604437
• 负责人: LEIGH PERREAULT
• 金额: $ 5.02万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604437
• 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 胰岛素抵抗定义为胰岛素刺激外周葡萄糖摄取以及抑制肝脏葡萄糖输出和脂肪分解的能力受损，是糖耐量受损 (IGT) 和 2 型糖尿病的主要特征。 胰岛素抵抗发生的机制尚不清楚。 骨骼肌是负责胰岛素对外周葡萄糖摄取作用的主要组织，因此被认为是胰岛素抵抗发展的主要部位。 特别是肌内甘油三酯 (IMTG) 含量和周转率，最近一直是人们广泛关注的话题，因为 IMTG 的量与胰岛素敏感性密切相关。 大量数据表明，健康男性和女性可能以不同方式使用 IMTG，尤其是在运动期间。 我们推测这种 IMTG 使用的性别依赖性机制在 IGT 的发展过程中消失了。 我们的第一个目标是描述患有 IGT 的男性和女性在基线和急性运动期间的 IMTG 含量和周转率。 该研究的第二个和第三个目标将试图解释男性和女性一旦发生 IGT 就失去转换 IMTG 能力的机制。 我们假设女性依赖于肌肉的氧化能力，而男性则依赖于 PPAR 靶基因的激活，正如动物研究中所显示的那样。 为了区分这些机制，患有 IGT 的男性和女性将被随机分配到运动训练计划（以增加氧化能力）或贝特疗法（以激活 PPAR，持续 12 周）。我们是否会结合血液和组织采样、稳定同位素方法和胰岛素敏感性测量来实现这些目标？更好地了解 IMTG 含量和周转率在男性和女性胰岛素抵抗发展中的作用可能会指导我们的治疗 糖尿病的预防和治疗。