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

骨骼肌和脂肪组织中葡萄糖转运的胰岛素反应相关分子的鉴定

基本信息

批准号：
14571091
负责人：
INOUE Gen
金额：
$ 2.18万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571091/
关键词：
insulin responsiveness adipocyte DNA chip transcriptional factor GLUT4 GLUT4 インスリン反応性

项目摘要

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.

我们使用3T3-L1细胞和3T3-C2细胞建立了诱导胰岛素敏感性的条件，例如脂肪细胞分化中GLUT4的定位、细胞内囊泡的诱导和GLUT4易位的增强。我们使用Affmetrix公司的DNA芯片检查了脂肪细胞分化的每个步骤中基因表达的变化。利用该技术，我们鉴定了在诱导高胰岛素敏感性时表达发生变化的基因。我们鉴定了大约 100-150 个已知基因，其表达增加或减少。我们发现了大约200-300个表达增加的EST。此外，根据这些基因表达谱，我们找到了与细胞内信号转导或转录调控有关的基因。我们使用蛋白质印迹或北方印迹检查了大鼠骨骼肌中基因的表达。我们鉴定了一种转录因子，其表达在 3T3-L1 细胞和 3T3-C2 细胞中诱导胰岛素敏感性时增加。该转录因子也在骨骼肌中表达。该因子在脂质代谢中发挥重要作用，并参与 GLUT4 囊泡中分子的调节。该分子可能连接脂肪细胞中的脂质代谢和碳水化合物代谢。我们致力于阐明该分子的生理作用。我们证实了与炎症、GTP结合蛋白、信号转导、细胞外基质有关的其他基因的表达变化。我们现在检查这些基因的表达是否受到脂肪细胞分化中已知的转录调节的调节。我们还研究了控制脂肪细胞分化的转录调控机制，这可能与 GLUT4 易位有关。