Identification of molecules implicated in insulin response of glucose transport in skeletal muscle and adinose tissue

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We established conditions for the induction of insulin sensitivity such as localization of GLUT4, induction of intracellular vesicle and enhancement of GLUT4 translocation in adipocyte differentiation using 3T3-L1 cells and 3T3-C2 cells. We examined changes of gene expression in each steps of adipocyte differentiation using DNA chips from Affmetrix company Using this technique, we identified genes the expression of which was changed on induction of high insulin sensitivity. We identified approximately 100-150 known genes the expression of which were increased or decreased. We found approximately 200-300 ESTs the expression of which were increased Furthermore, on the basis of these gene expression profiles, we picked up the genes implicated in intracellular signal transduction or transcriptional regulation. We checked the expression of the genes using Western blot or Northern blot in rat skeletal muscle. We identified one transcriptional factor the expression of which was increased on induction of insulin sensitivity in 3T3-L1 cells and in 3T3-C2 cells. This transcriptional factor was expressed also in skeletal muscle. This factor plays an important role in lipid metabolism, and is implicated in regulation of a molecule in GLUT4 vesicle. This molecule may connect lipid metabolism and carbohydrate metabolism in adipocyte. We are engaged in elucidation of physiological role of the molecule. We confirmed the change of expression of other genes which are implicated in inflammation, in GTP-binding protein, in signal transduction, extracellular matrix. We now examine whether these the expression of these genes are regulated by known transcriptional regulation in adipocyte differentiation. We also investigate mechanism of transcriptional regulation controlling adipocyte differentiation which may implicated GLUT4 translocation.