Gene Expression Profiling On Insulin Resistance & Obesit

我们进行了全球基因表达谱分析，以补充正在进行的定位克隆工作，以确定糖尿病及其预测因素、胰岛素抵抗和肥胖症的易感基因。为此，我们使用差异显示聚合酶链式反应和包含6,800个基因和35000个表达序列标签(EST)的人类寡核苷酸微阵列，检测了非糖尿病全血皮马印第安人的组织样本中的基因表达谱。 为了确定胰岛素抵抗的可能决定因素，独立于肥胖的影响，从一组同样肥胖的PIMA的骨骼肌样本中识别出差异表达的基因，这些PIMA与肥胖、年龄和性别匹配。为了确定肥胖的可能决定因素，我们从一组年龄和性别匹配的严重肥胖和瘦PIMA中鉴定了分离的、皮下和腹部脂肪细胞中差异表达的基因。为了识别潜在的二次差异表达的基因(例如，由于高胰岛素血症)，我们 还测定了从这些相同的脂肪组织样本中培养的前脂肪细胞中的基因表达水平。

We performed global gene expression profiling to complement the ongoing positional cloning effort to identify susceptibility genes for diabetes and its predictors, insulin resistance and obesity. To this end, we have examined gene expression profiles in tissue samples from non-diabetic full-blooded Pima Indians using differntial-display PCR and human oligonucleotide microarrays containing 6800 genes and 35000 expressed sequence tags (ESTs). To identify possible determinants of insulin resistance, independent of the effects of obesity, differentially expressed genes were identified in skeletal muscle samples from a group of equally obese Pimas, matched for obesity, age and sex. To identify possible determinants of obesity, we identified differentially expressed genes in isloated, subcutaneous, abdominal adipocytes from a group of severly obese and lean Pimas matched for age and sex. To identify genes that were potentially secondarily differentially expressed, (e.g. as a result of hyperinsulinemia), we also determined leveles of gene expression in pre-adipocytes grown from these same adipose tissue samples.