MECHANISMS OF HUMAN INSULIN RESISTANCE: ROLE OF LIPID METABOLISM

人类胰岛素抵抗的机制：脂质代谢的作用

• 批准号: 7380429
• 负责人: W Timothy GARVEY
• 金额: $ 4万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7380429
• 关键词: MECHANISMS; HUMAN; INSULIN; RESISTANCE; ROLE

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. The insulin resistance syndrome provides the "common soil" for the development of Type 2 Diabetes and Cardiovascular Disease and is responsible for extensive morbidity and mortality in our society. The overall aims of this study are to better define these abnormalities in fat metabolism and their relationship to the development of IR. These in-vivo studies will define the relationship between FFA turnover, lipid oxidation, IR, and provide a functional basis for interpreting the molecular data. Subjects characterized with IR such as obesity, impaired glucose tolerance, hyperlipidemia, and/or diabetes will be recruited for study. Admitted to the GCRC, subjects will undergo preliminary medical history, physical exam, EKG, blood pressure and blood/urine labs, followed by a series of metabolic studies to measure body composition, energy expenditure, glucose tolerance, in vivo insulin sensitivity and glucose metabolism, insulin secretion, and lipid metabolism. They will then be placed on a very low calorie diet for 1 week and repeat the series of metabolic study. Once completed, the subjects will enter phase 3 being placed on a weight loss diet of 1200-1800 calories/day and monitored in the outpatient GCRC until 15% of initial body weight is lost. Subjects will return to GCRC inpatient for a repeat of the metabolic studies, as described in phases 1 and 2. Molecular measurements in fat and muscle tissue will be analyzed with enzyme assay, western blot, mRNA quantification, subfractionation, cDNA microarray, and proteomics.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。胰岛素抵抗综合征为2型糖尿病和心血管疾病的发展提供了“共同的土壤”，并在我们的社会中造成了广泛的发病率和死亡率。这项研究的总体目标是更好地确定这些脂肪代谢异常及其与胰岛素抵抗发展的关系。这些体内研究将确定FFA周转、脂质氧化、IR之间的关系，并为解释分子数据提供功能基础。具有胰岛素抵抗特征的受试者，如肥胖、糖耐量受损、高脂血症和/或糖尿病将被招募为研究对象。进入GCRC后，受试者将接受初步病史、体格检查、心电图、血压和血/尿实验室检查，然后进行一系列代谢研究，以测量身体成分、能量消耗、葡萄糖耐量、体内胰岛素敏感性和葡萄糖代谢、胰岛素分泌和脂肪代谢。然后，他们将被安排在非常低卡路里的饮食中持续一周，并重复一系列的代谢研究。一旦完成，受试者将进入第三阶段，每天摄入1200-1800卡路里的减肥饮食，并在门诊GCRC进行监测，直到初始体重减少15%。受试者将返回GCRC住院患者进行重复的代谢研究，如第一阶段和第二阶段所述。脂肪和肌肉组织的分子测量将通过酶分析、蛋白质印迹、信使核糖核酸定量、亚分离、基因芯片和蛋白质组学进行分析。