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: 7606311
• 负责人: Nicola Abate
• 金额: $ 0.52万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7606311
• 关键词: Age; Asian Indian; Biochemical; Biological; Body fat; Cardiovascular Diseases; Caucasians; Caucasoid Race; Coagulation Process; Computer Retrieval of Information on Scientific Projects Database; Condition; Defect; Development; Diabetes Mellitus; Dyslipidemias; Esterified Fatty Acids; Ethnic group; Evaluation; Funding; Genes; Genetic; Genetic Determinism; Genetic Polymorphism; Genetic Predisposition to Disease; Glucose Intolerance; Grant; Hypertension; Incidence; Individual; Institution; Insulin; Insulin Resistance; Insulin Signaling Pathway; Location; Metabolic; Metabolic syndrome; Obesity; Pathogenesis; Plasma; Research; Research Personnel; Resources; Role; Secondary to; Source; United States National Institutes of Health; gene interaction; insulin sensitivity; response

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.

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。 胰岛素抵抗是一种以生物学反应对外源性或内源性胰岛素的反应受损的疾病，已被认为是代谢综合征发展的主要因素（动脉粥样硬化血脂异常，高血压，葡萄糖不耐症，凝结缺陷）和心血管疾病。 胰岛素抵抗发展所涉及的机制尚不完全了解。 我们以前的研究旨在定义肥胖，体内脂肪分布和胰岛素抵抗之间的关系。 我们的研究表明，对于肥胖的任何特定程度或位置，胰岛素敏感性都有很大的差异，这表明内源性（遗传）因子也有助于胰岛素抵抗。 为了更好地评估遗传倾向在与肥胖相关胰岛素耐药性变异性方面的作用，我们现在建议研究来自印度次大陆（亚洲印第安人）的个体。 与高加索人相比，这个族裔群体的心血管疾病和糖尿病的发生率高四倍，而高加索人似乎与过度胰岛素抵抗密切相关。 几项研究表明，即使没有肥胖症，亚洲印第安人也过度胰岛素耐药性，这可能是“遗传易感性”的继发性。 因此，亚洲印第安人体内脂肪 - 基因相互作用的评估似乎是一种理想的方法，可以挑剔基因在胰岛素抵抗的发病机理中的作用，而与肥胖，年龄或身体不活跃等已知的混杂因素无关。 本研究的重点是代谢/生化决定因素[体内脂肪含量和血浆脂肪酸的血浆水平（NEFA）（NEFA）（NEFA）和遗传倾向（调节基因的多态性（调节胰岛素符号途径的近端段）的基因），作为胰岛素耐胰岛素抗性的机制。