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

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NIDDM is primarily caused by the insulin resistance, and increase insulin secretion from pancreatic β-cells and sub-sequently deficiency of insulin. Therefore it is a key to find a substance for insulin resistance in the blood of the patient. There are several substrates in the plasma for insulin resistance, TGF-β, leptin and resistine. However, they are uncertain for insulin resistance of the onset of NIDDM.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 which is one of the most important physiological effect of insulin. We developed a highly sensitive and quantitative method to detect GLUT4 immunologically on the surface of intact cells, using c-myc epitope-tagged GLUT4 (GLUT4myc). We established stable clones to express GLUT4myc in 3T3L1 adipocytes and established the transgenic rat expressing GLUT4myc in rat adipocytes. We have developed a simple and new method to screen the compounds for triggering the GLUT4myc translocation in 96 wells using luminescence method. This method is useful for the first screening for finding the substances for insulin resistance. Recently, we found a part of known molecule may be the substance for insulin resistance.