MOLECULAR GENETICS OF INSULIN RESISTANCE AND NONINSULIN-DEPENDENT DIABETES

胰岛素抵抗导致包括肥胖和2型糖尿病在内的多种疾病的发病机制。我们已经研究了导致胰岛素抵抗的遗传因素的本质。以前，我们已经确定了与胰岛素抵抗相关的几种遗传综合征患者的胰岛素受体基因突变。最近，我们一直在对各种形式的脂肪萎缩患者进行临床研究，其中大多数患者还患有胰岛素抵抗性糖尿病。与Dr. A合作。Garg和A. Bowcock（德克萨斯西南大学），先天性全身性脂肪萎缩的基因已定位于染色体9 q34。此外，我们已经证明曲格列酮治疗可以显著改善脂肪萎缩性糖尿病患者的代谢控制。在随访过程中，我们还将确定曲格列酮是否会导致体脂增加。目前正在努力开发新的方案，以评估新的治疗药物（包括罗格列酮，吡格列酮和瘦素）的潜在益处。- 胰岛素，胰岛素抵抗，胰岛素受体，酪氨酸磷酸化，糖尿病，脂肪萎缩，邓尼根综合征，曲格列酮-人类受试者

Insulin resistance contributes to the pathogenesis of several disease states including obesity and type 2 diabetes mellitus . We have investigated the nature of the genetic factors that predipose to the development of insulin resistance. Previously, we have identified mutations in the insulin receptor gene in patients with several genetic syndromes associated with insulin resistance. More recently, we have been carrying out clinical investigation of patients with various forms of lipoatrophy, most of whom also have insulin resistant diabetes. In collaboration with Drs. A. Garg and A. Bowcock (Univ. Texas Southwestern), the gene for congenital generalized lipoatrophy has been mapped to chromosome 9q34. In addition, we have demonstrated that troglitazone therapy dramatically improves metabolic control in patients with lipoatrophic diabetes. In the course of follow-up, we will also determine whether troglitazone leads to an increase in body fat. Efforts are underway to develop new protocols to evaluate the potential benefit of newer therapeutic agents (including rosiglitazone, pioglitazone, and leptin). - insulin, insulin resistance, insulin receptor, tyrosine phosphorylation, diabetes, lipoatrophy, Dunnigan's syndrome, troglitazone - Human Subjects