Development of a simple screening system for the discovery of a new drug for diabetes

目前有500多万糖尿病患者，必须开发一种新的口服药物。然而，目前还没有一种简单、定量的方法来寻找口服糖尿病药物。以往的降血糖新药的筛选是采用整体动物法，但这种方法不适合于大量筛选化合物。4型葡萄糖转运蛋白（GLUT 4）从细胞内转运至细胞表面是胰岛素刺激胰岛素靶细胞葡萄糖摄取的主要机制。我们建立了一种高灵敏度和定量检测GLUT 4在完整细胞表面的免疫学方法，使用c-myc表位标记的GLUT 4（GLUT 4 myc）。我们建立了稳定的克隆表达GLUT 4 myc在CHO，L 6成肌细胞和3 T3 L1脂肪细胞。我们发展了一种简单的新方法，用发光素法在96个威尔斯孔中筛选触发GLUT 4 myc易位的化合物。该方法可用于糖尿病口服新药的初步筛选。

There are more than 5 million patients of diabetes and a new oral drug must be developed. However, there is not a simple and quantitative method to find the oral diabetic drug. Whole animal was used to find the new drug to estimate the decrease of blood glucose level, but this method is not adeguate toscreen a large number of compound. Translocation of the type 4 glucose transporter (GLUT4) to the cell surface from an intracellular pool is the major mechanism of insulin-stimulated glucose uptake in insulin-target cells. We developed a highly sensitive and quantitative method of detect GLUT4 immunologically on the surface of intact cells, using c-myc epitope-tagged GLUT4 (GLUT4myc). We established stable clones to express GLUT4myc in CHO,L6 myoblasts and 3T3L1 adipocytes. We have developed a simple and new method to screen the compounds for triggering the GLUT4myc translocation in 96 wells using luminessence method. This method is useful for the first screening for developing a new oral drug for diabetes.