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BIOLOGICAL ROLES OF NEW TRANSCRIPTION FACTOR FOR GLUCOSE METABOLISM(ChREBP) IN PANCREATIC ISLET CELLS

新的葡萄糖代谢转录因子（ChREBP）在胰岛细胞中的生物学作用

基本信息

批准号：
15590963
负责人：
KAWAGUCHI Takumi
金额：
$ 2.24万
依托单位：
KURUME UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590963/
关键词：
ChREBP INS-1 cell insulin secretion gene mutation insulin receptor diabetes mellitus HepG2 cell insulin receptor substrate リン酸化肝細胞 insulin receptor substrate 1 2 2型糖尿病 INS-1細胞 Nuclear localization signal 細胞内局在変化 siRNA イン

项目摘要

Diabetes mellitus is characterized by the impairment of glucose metabolism, however, the responsible molecules for the development of diabetes mellitus remains unclear. Recently, we have identified and characterize a transcription factor for glucose metabolism, carbohydrate responsive element binding protein(ChREBP). ChREBP activates the transcripton of liver-type pyruvate kinase gene. The aim of this study is to investigate the biological roles of ChREBP in pancreatic beta cell and hepatocytes, target cells of insulin.The role of ChREBP in insulin secretion was investigated by using INS-1 cells. By transfection of ChREBP gene into INS-1 cell, ChREBP was overexpressed in INS-1 cell and insulin levels in culture media was altered. We also examined the mutation of ChERBP gene in patients with diabetes mellitus. Although regulation sites of ChREBP were investigated, any mutation of gene was not identified. In addition, we investigated the mechanisms for hepatic insulin resistance. Although there was no significant change in insulin receptor, down-regulation of hepatic insulin receptor substrate 1/2, central molecules for intracellular insulin signaling cascade, was seen in HepG2 cells showing increased insulin resistance.In this study, we demonstrated the biological roles of ChREBP in INS-1 cells and the involvement of hepatocyte, a target cell of insulin, in the development of insulin resistance. Thus, ChREBP and insulin receptor substrate 1/2 may be responsible molecules for the development of diabetes mellitus.

糖尿病是以糖代谢障碍为特征的疾病，但其发病机制尚不清楚。最近，我们已经确定并表征了葡萄糖代谢的转录因子，碳水化合物反应元件结合蛋白（ChREBP）。ChREBP激活肝型丙酮酸激酶基因的转录。本研究旨在探讨ChREBP在胰岛素靶细胞--胰岛β细胞和肝细胞中的生物学作用，以INS-1细胞为研究对象，探讨ChREBP在胰岛素分泌中的作用。通过将ChREBP基因转染INS-1细胞，ChREBP在INS-1细胞中过表达，并改变培养液中的胰岛素水平。同时检测了糖尿病患者ChERBP基因的突变情况。虽然研究了ChREBP的调控位点，但未发现任何基因突变。此外，我们还研究了肝脏胰岛素抵抗的机制。虽然胰岛素受体没有明显变化，但在胰岛素抵抗增加的HepG 2细胞中观察到肝胰岛素受体底物1/2（细胞内胰岛素信号级联的中心分子）的下调。因此，ChREBP和胰岛素受体底物1/2可能是糖尿病发生发展的责任分子。

项目成果

期刊论文数量（36）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The Wilson disease protein ATP7B resides in the late endosomes with rab7 and the Niemann-Pick C1 protein

DOI：
10.1016/s0002-9440(10)62272-9
发表时间：
2005-02-01
期刊：
AMERICAN JOURNAL OF PATHOLOGY
影响因子：
6
作者：
Harada, M;Masaru, H;Sata, M
通讯作者：
Sata, M

Endothelial progenitor cell transplantation improves the survival following liver injury in mice

DOI：
10.1053/j.gastro.2005.10.050
发表时间：
2006-02-01
期刊：
GASTROENTEROLOGY
影响因子：
29.4
作者：
Taniguchi, E;Kin, M;Sata, M
通讯作者：
Sata, M

Cholestasis in a rat model of graft-versus-host disease is accompanied by alteration of the expression and distribution of tight-junction-associated proteins.

DOI：
10.3892/ijmm.15.3.431
发表时间：
2005-03
期刊：
International journal of molecular medicine
影响因子：
5.4
作者：
K. Sasatomi;S. Sakisaka;T. Kawaguchi;S. Hanada;E. Taniguchi;H. Koga;M. Harada;M. Sata
通讯作者：
K. Sasatomi;S. Sakisaka;T. Kawaguchi;S. Hanada;E. Taniguchi;H. Koga;M. Harada;M. Sata

Keratin-containing inclusions affect cell morphology and distribution of cytosolic cellular components.

含角蛋白的内含物影响细胞形态和细胞质细胞成分的分布。

DOI：
10.1016/j.yexcr.2004.12.009
发表时间：
2005
期刊：
Experimental cell research.
影响因子：
0
作者：
Hanada,Shinichiro;Harada,Masaru;Kumemura,Hiroto;Omary,MBishr;Kawaguchi,Takumi;Taniguchi,Eitaro;Koga,Hironori;Yoshida,Takafumi;Maeyama,Michiko;Baba,Shinji;Ueno,Takato;Sata,Michio
通讯作者：
Sata,Michio

Causal relationship between hepatitis C virus core and the development of type 2 diabetes mellitus in a hepatitis C virus hyperendemic area : a pilot study.

丙型肝炎病毒高流行地区丙型肝炎病毒核心与 2 型糖尿病发展之间的因果关系：一项试点研究。