Molecular mechanisms of Insulin signal transduction and diabetes mellitus

胰岛素信号转导与糖尿病的分子机制

• 批准号: 20390095
• 负责人: EBINA Yousuke
• 金额: $ 12.56万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390095/
• 关键词: 分子病態学; インスリンシグナル伝達; インスリン作用; GLUT4; TUG; sIR; 高血糖; 超高感度sIR測定法; シグナル伝達; BFA; GLUT4トランスロケーション; ARF; BIG2

Akt substrate of 160kDa (AS160) is a Rab GTPase activating protein (GAP) and was recently identified as a component of the insulin signaling pathway of glucose transporter type 4 (GLUT4) translocation. We and others, previously reported that the activation of Galphaq protein-coupled receptors (GalphaqPCRs) also stimulated GLUT4 translocation and glucose uptake in several cell lines. Here, we report that the activation of GalphaqPCRs also promoted phosphorylation of AS160 by the 5'-AMP activated proteinkinase (AMPK). Rat 3Y1 cells lacking AS160 did not show insulin-induced GLUT4 translocation. The cells stably expressing GLUT4 revealed GLUT4 vesicles that were mainly localized in the perinuclear region and less frequently on the cell surface. After expression of exogenous AS160, GLUT4 on the cell surface decreased and GLUT4 vesicles were redistributed throughout the cytoplasm. Although PMA-induced or sodium fluoride-induced GLUT4 translocation was significantly increased in these cells, insulin did not affect GLUT4 translocation. These results suggest that AS160 is a common regulator of insulin-and GalphaqPCR activation-mediated GLUT4 distribution in the cells.

Akt底物160 kDa（AS 160）是一种Rab GT3激活蛋白（GAP），最近被鉴定为葡萄糖转运蛋白4（GLUT 4）转位的胰岛素信号通路的一个组分。我们和其他人先前报道了Galphaq蛋白偶联受体（GalphaqPCR）的激活也刺激了几种细胞系中的GLUT 4易位和葡萄糖摄取。在这里，我们报告GalphaqPCR的激活也促进了5 '-AMP激活的蛋白激酶（AMPK）对AS 160的磷酸化。缺乏AS 160的大鼠3 Y1细胞未显示胰岛素诱导的GLUT 4易位。稳定表达GLUT 4的细胞显示GLUT 4囊泡主要位于核周区域，较少出现在细胞表面。外源性AS 160表达后，细胞表面GLUT 4减少，GLUT 4囊泡重新分布于整个细胞质。虽然PMA诱导或氟化钠诱导的GLUT 4易位在这些细胞中显着增加，胰岛素不影响GLUT 4易位。这些结果表明，AS 160是细胞中胰岛素和GalphaqPCR激活介导的GLUT 4分布的常见调节因子。

项目成果

A novel ultra-sensitive enzyme immunoassay for soluble human insulin receptor ectodomain and its measurement in urine from healthy subjects and patients with diabetes mellitus

一种新型超灵敏酶联免疫分析方法，用于检测可溶性人胰岛素受体胞外域及其在健康受试者和糖尿病患者尿液中的测量

• 发表时间: 2009
• 期刊: Clinical Biochemistry 42(13-14)
• 作者: Mori T;Nagamura-Inoue T;et al.;Umehara A.
• 通讯作者: Umehara A.

Soluble insulin receptor ectodomain level was elevated in the plasma of cancer patients

癌症患者血浆中可溶性胰岛素受体胞外域水平升高

• 发表时间: 2009
• 作者: Yuasa T. et.;al.
• 通讯作者: al.

可溶化インスリン受容体細胞外ドメイン(sIR)は癌患者血清中で増加している

癌症患者血清中可溶性胰岛素受体胞外结构域 (sIR) 增加

• 发表时间: 2009
• 作者: 湯浅智之;小畑利之;矢野聖二;岡本英治;西岡安彦;久保宜明;高橋正幸;中逵弘能;長屋寿雄;金山博臣;荒瀬誠治;曽根三郎;蛯名洋介
• 通讯作者: 蛯名洋介

Soluble insulin receptor ectodomain in the plasma is a possible broad-spectrum tumor marker

血浆中的可溶性胰岛素受体胞外域是一种可能的广谱肿瘤标志物

• 发表时间: 2009
• 作者: Yuasa T. et.;al.
• 通讯作者: al.

The Rab GTPase-Activating Protein AS160 as A Common Regulator of Insulin- and Gq-Mediated Intracellular GLUT4 Vesicle DistributionA

Rab GTP 酶激活蛋白 AS160 作为胰岛素和 Gq 介导的细胞内 GLUT4 囊泡分布的共同调节剂A

• 发表时间: 2009
• 期刊: Endocrine Journal Vol.56, No.3
• 作者: Yuasa Tomoyuki;Uchiyama Keiji;Yuko OGURA;Kimura Masafumi;Kiyoshi TESHIGAWARA;Hosaka Toshio;Yoshinori TANAKA;Obata Toshiyuki;Hiroyuki SANO;Kishi Kazuhiro;Ebina Yousuke
• 通讯作者: Ebina Yousuke