Development of a drug for diabetes using human genome information

越来越多的证据表明，多基因因素参与了非胰岛素依赖型糖尿病(NIDDM)的发病机制，但遗传缺陷的性质尚不清楚。NIDDM的常见形式是一种异质性疾病，其中至少有两个主要缺陷与表型的病理生理有关：胰岛素缺乏和胰岛素抵抗。胰岛素通过将葡萄糖转运蛋白4(GLUT4)从细胞内池转移到质膜上，刺激血糖进入骨骼肌和脂肪组织，从而在体内迅速降低血糖水平。胰岛素这一作用的失败似乎是2型糖尿病的主要原因之一。磷脂酰肌醇3-激酶(PI-3-Kinase)和AKT在胰岛素刺激葡萄糖转运中起关键作用，但具体机制尚不清楚。其目的是阐明Akt后新的信号因子，并开发刺激胰岛素信号传导的药物。利用蛋白质组学方法对Akt2的PH结构域结合蛋白进行了分析，发现了一些可能参与胰岛素信号转导的因素

Evidence suggesting that polygenetic factors contribute to the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) is accumulating, but the nature of the genetic defect is unknown. The common form of NIDDM is a heterogeneous disorder in which at least two major defects contribute to the pathophysiology of the phenotype : insulin deficiency and insulin resistance. Insulin stimulates the disposal of blood glucose into skeletal muscles and adipose tissues by the translocation of glucose transporter type4 (GLUT4) from intracellular pools to the plasma membrane, and consequently the concentration of blood glucose levels decreases rapidly in vivo. Failure of this action of insulin seems to be one of the major causes of Type2 diabetes. Phosphatidylinositol 3-kinase (PI 3-kinase) and AKT play a pivotal role in the stimulation of glucose transport by insulin, but detailed mechanisms are unknownDur aim is to elucidate the new signalling factors after Akt and to develop the drug to stimulate the insulin signalling. we analyzed the proteins which bind to the PH domain of Akt2 using proteome analysis and found some factors which may participate the insulin signalling