METABOLIC AND GENETIC DETERMINANTS OF INSULIN RESISTANCE

胰岛素抵抗的代谢和遗传决定因素

• 批准号: 7377602
• 负责人: Nicola Abate
• 金额: $ 3.04万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377602
• 关键词: METABOLIC; GENETIC; DETERMINANTS; INSULIN; RESISTANCE

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, a condition characterized by impaired biological response to either exogenous or endogenous insulin, has been implicated as a major factor in the development of the metabolic syndrome (atherogenic dyslipidemia, hypertension, glucose intolerance, coagulation defects) and cardiovascular disease. The mechanisms involved in the development of insulin resistance are not entirely understood. Our previous studies have been directed towards defining the relations among obesity, body fat distribution and insulin resistance. Our studies revealed that for any given degree or location of obesity, there is considerable variability in insulin sensitivity, suggesting that endogenous (genetic) factors also contribute importantly to insulin resistance. To better evaluate the role of genetic predisposition on the variability of obesity-related insulin resistance, we now propose to study individuals from the Indian Subcontinent (Asian Indians). This ethnic group has a fourfold higher incidence of cardiovascular disease and diabetes than Caucasians, seemingly closely associated with excessive insulin resistance. Several studies have indicated that Asian Indians are excessively insulin resistant even in the absence of obesity, and this is probably secondary to "genetic predisposition". Therefore, the evaluation of body fat-gene interaction in Asian Indians seems to be an ideal approach to single out the role of genes in the pathogenesis of insulin resistance, independently of known confounding factors, such as obesity, age or physical inactivity. The present study focuses on the interaction between metabolic/biochemical determinants [body fat content and plasma levels of non-esterified fatty acids (NEFA) and genetic predisposition (polymorphism of genes regulating the proximal segment of the insulin-signaling pathway) as a mechanism for the development of insulin resistance.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。胰岛素抵抗是一种以对外源性或内源性胰岛素的生物反应受损为特征的疾病，已被认为是代谢综合征（动脉粥样硬化性血脂异常、高血压、葡萄糖耐受不良、凝血缺陷）和心血管疾病发展的一个主要因素。胰岛素抵抗发生的机制尚不完全清楚。我们之前的研究一直致力于确定肥胖、体脂分布和胰岛素抵抗之间的关系。我们的研究表明，对于任何特定程度或位置的肥胖，胰岛素敏感性都有相当大的可变性，这表明内源性（遗传）因素也对胰岛素抵抗起重要作用。为了更好地评估遗传易感性对肥胖相关胰岛素抵抗变异性的作用，我们现在建议研究来自印度次大陆（亚洲印度人）的个体。这个族群的心血管疾病和糖尿病的发病率是白种人的四倍，似乎与过度胰岛素抵抗密切相关。几项研究表明，即使没有肥胖，亚洲印度人也会过度胰岛素抵抗，这可能是继发于“遗传易感性”。因此，对亚洲印度人体内脂肪-基因相互作用的评估似乎是一种理想的方法，可以独立于已知的混杂因素，如肥胖、年龄或缺乏运动，找出基因在胰岛素抵抗发病机制中的作用。本研究的重点是代谢/生化决定因素[体脂肪含量和血浆非酯化脂肪酸（NEFA）水平]与遗传易感性（调节胰岛素信号通路近端片段的基因多态性）之间的相互作用作为胰岛素抵抗发展的机制。