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Molecular mechanism of insulin-induced activation of glucose transport

胰岛素诱导葡萄糖转运激活的分子机制

基本信息

批准号：
03670130
负责人：
KASAHARA Michihiro
金额：
$ 1.28万
依托单位：
TEIKYO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670130/
关键词：
Insulin Glucose Transporter Adipocyte Placenta Recycling Translocation Insulin-like growth factor-I グルコ-ス輸送 GLUT1 SGLT1 腎臓

项目摘要

Significant advance has been achieved in the study of insulin action. Successful cloning of the insulin receptor had been reported. It has become clear that some patients with insulin-independent diabetes mellitus possess mutant insulin receptors. At the same time, an unexpected insulin-induced translocation of intracellular glucose transporter to plasma membrane has been implicated as a cause for insulin-induced activation of glucose transport.We have proceed further on the study of glucose transporter translocation and extended the wide-ranged study of insulin reception and the cell biological study on the glucose transporter. The following is the major achivement we have made in this study.1. We compared the time course of activation of glucose transport and the time course of GLUT1 & GLUT4 translocation in rat adipocytes. Transport activity and GLUT1 translocation showed a similar time course, on the other hand, GLUT4 translocation was slower. These results are suggestive of the importance of GLUT1 in the insulin action, which is apparently against a popular view of GLUT 4 preference.2. Insulin-like growth factor-I(IGF-1) receptor was purified from human placenta. Rabbit antibody against the IGF-I receptor was raised. Tissues from patients with breast cancer showed elevated level of the IGF-I receptor, which is in accord with the observation that IGF-I binding activity is high in these tissues.3. Immunofluoresent and immunoelectron microscopic studies revealed the GLUT1 transporter is abundant in the blood-tissue barriers such as the blood-brain barrier, the blood-ocular barrier and the placental barrier. Using similar techniques, SGLT1, a major Na-dependent glucose transporter is localized to the brush border membranes of small intestine and the proximal tubules of kidney, which is in concert with physiological observations.

胰岛素作用的研究已取得重大进展。已经报道了成功克隆胰岛素受体。已经清楚的是，一些胰岛素非依赖型糖尿病患者具有突变的胰岛素受体。同时，胰岛素诱导的细胞内葡萄糖转运蛋白向质膜的转位被认为是胰岛素诱导的葡萄糖转运激活的一个原因，我们对葡萄糖转运蛋白转位的研究进一步深入，拓展了胰岛素受体的广泛研究和葡萄糖转运蛋白的细胞生物学研究。以下是我们在这项研究中取得的主要成果.我们比较了大鼠脂肪细胞葡萄糖转运激活的时间过程和GLUT 1和GLUT 4易位的时间过程。转运活性与GLUT 1转运的时间进程相似，而GLUT 4转运的时间进程较慢。这些结果提示GLUT 1在胰岛素作用中的重要性，这显然与GLUT 4偏好的流行观点相反。从人胎盘中分离纯化胰岛素样生长因子-I（IGF-1）受体。兔抗IGF-I受体抗体的产生。乳腺癌患者的组织中IGF-I受体水平升高，这与IGF-I在这些组织中具有高结合活性的观察结果雅阁.免疫荧光和免疫电镜研究表明，GLUT 1转运蛋白在血脑屏障、血眼屏障和胎盘屏障等血组织屏障中含量丰富。使用类似的技术，SGLT 1（一种主要的钠依赖性葡萄糖转运蛋白）定位于小肠刷状缘膜和肾脏近端小管，这与生理学观察结果一致。