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.

我们确定了诱导胰岛素敏感性的条件，例如使用3T3-L1细胞和3T3-C2细胞在脂肪细胞分化中诱导GLUT4的定位，细胞内囊泡的诱导和GLUT4易位的增强。我们使用此技术利用AFFMetrix公司的DNA芯片在脂肪细胞分化的每个步骤中检查了基因表达的变化，我们确定了基因在诱导高胰岛素敏感性的诱导时会改变其表达。我们确定了大约100-150个已知基因的表达增加或降低。我们发现大约200-300 ests的表达增加了，根据这些基因表达谱，我们拾取了与细胞内信号转导或转录调控有关的基因。我们在大鼠骨骼肌中使用蛋白质印迹或北印迹检查了基因的表达。我们鉴定出一个转录因子在3T3-L1细胞和3T3-C2细胞中胰岛素敏感性诱导时的表达增加。该转录因子在骨骼肌中也表示。该因素在脂质代谢中起着重要作用，并且与GLUT4囊泡分子的调节有关。该分子可以将脂质代谢和碳水化合物代谢连接起来。我们参与阐明该分子的生理作用。我们证实了其他基因的表达变化，这些基因与炎症有关，在GTP结合蛋白，信号转导，细胞外基质中。现在，我们检查这些基因的表达是否通过脂肪细胞分化中已知的转录调节调节。我们还研究了控制脂肪细胞分化的转录调控机制，这可能暗示GLUT4易位。