Gene Expression Profiling On Insulin Resistance And Obesity

胰岛素抵抗和肥胖的基因表达谱

• 批准号: 8349898
• 负责人: Clifton Bogardus
• 金额: $ 122.43万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8349898
• 关键词: Adipose tissue; Age; Arizona; Autoimmune Process; Blood; Body Composition; Complement; DNA; Data; Data Analyses; Diabetes Mellitus; Disease; Elements; Euglycemic Clamping; Exons; Functional disorder; Gene Expression; Gene Expression Profiling; Genes; Genetic; Genome; Glucose Clamp; HLA-DRB1; High Prevalence; Incidence; Insulin; Insulin Resistance; Molecular Profiling; Native Americans; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Phenotype; Pima Indian; Population; Predisposition; Prevalence; Regulation; Reporting; Single Nucleotide Polymorphism; Skeletal Muscle; Susceptibility Gene; Tissue Sample; Transcript; Work; base; follow-up; genome wide association study; glucose production; in vivo; insulin secretion; non-diabetic; positional cloning; volunteer

We are performing global exon expression profiling to complement the ongoing positional cloning effort to identify susceptibility genes for diabetes and its predictors, insulin resistance, insulin secertory dysfunction and obesity. To this end, we are examining exon expression profiles in tissue samples from non-diabetic full-blooded Pima Indians using Affymetrix exon arrys that query over 1 million known and predicted exons across the entire genome. We have collected 225 skeletal muscle tissue samples and 250 adipose tissue samples from non-diabetic Pima Indians who have been metabolically phenotyped for body composition and insulin action in vivo using the hyperinsulinemic euglycemic clamp. Follow up data is available on the diabtic status of most of these volunteers, up to 7-10 years later, so will be able to identify a prediabtic exon expression profile in this population. We have completed the exon arrays on all skeletal muscle and adipose tissue samples and are currently analyzing these data and comparing to genotypic data collected on many of the subjects from our genome-wide association study using single nucleotide polymorphisms. Initial analyses ahve identified several trancripts with a bimodal distribuiton apparently due to cis acting DNA elements. One of these transcripts was HLA-DRB1 and levels of this trancript were associated with early insulin secretion indicating an autoimmune regulation of insulin secretion in this population.

我们正在进行全局外显子表达分析，以补充持续的位置克隆努力，以鉴定糖尿病及其预测因素，胰岛素抵抗，胰岛素分离功能障碍和肥胖的易感基因。为此，我们使用Affymetrix Exon Arrys检查了来自非糖尿病全血PIMA印第安人的组织样品中的外显子表达谱，这些外显子Arrys询问了整个基因组中已知超过100万个已知和预测外显子。 我们收集了225个骨骼肌组织样品和250个脂肪组织样品 来自已代谢表型的非糖尿病PIMA印第安人，使用高胰岛素优美糖夹在体内进行体内和胰岛素作用。后续数据可用于大多数这些志愿者的糖尿病状况，最多7-10年后，因此能够识别该人群中的增头外显子表达谱。我们已经完成了所有骨骼肌和脂肪组织样品上的外显子阵列，目前正在分析这些数据，并与使用单核苷酸多态性从我们全基因组关联研究中收集的许多受试者收集的基因型数据进行了比较。 初步分析AHVE鉴定了几个带有双峰分布的trancripts，显然是由于顺式作用DNA元素引起的。这些成绩单之一是HLA-DRB1，该Trancript的水平与早期胰岛素分泌有关，表明该人群中胰岛素分泌的自身免疫性调节。