Studies on the molecular basis of insulin actions

胰岛素作用的分子基础研究

• 批准号: 05044171
• 负责人: KASUGA Masato
• 金额: $ 5.76万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05044171/
• 关键词: Insulin; GLUT; PI 3-kinase; 膜ラッフル形成

In collaboration with Professor M.Waterfield in London, we found phosphoinositide 3-kinases associated with IRS-1 mediate the stimulatory effect of insulin on the glucose transport (translocation of glucose transporters) and membrane ruffling. We also found that an adaptor protein Nck, which binds to IRS-1, associates two proteins of 116kDa and 130kDa in vitro. The amino acid sequence of these proteins was analyzed in Professor Waterfield's laboratory and we cloned the cDNA of these two proteins.In collaboration with Professor G.Holman in Bath, we found that wortmannin, an inhibitor of phosphoinositide 3-kinase, inhibits the stimulatory effect of insulin on glucose transport (translocation of GLUT4 from cytosols to plasma membranes) in 3T3-L1 adipocytes. Furthermore, we analyzed the kinetics of GLUT4 in the presence of wortmannin and insulin and concluded that wortmannin inhibited the stimulatory effect of insulin on the exocytosis, but not the endocytosis, of GULT4 in 3T3-L1 adipocytes.

与伦敦的M.Waterfield教授合作，我们发现与IRS-1相关的磷酸肌醇3-激酶介导胰岛素对葡萄糖转运（葡萄糖转运蛋白的易位）和膜皱褶的刺激作用。我们还发现一个与IRS-1结合的接头蛋白Nck在体外可与116 kDa和130 kDa两种蛋白结合。我们与巴斯的G.Holman教授合作，发现磷酸肌醇3-激酶的抑制剂渥曼青霉素（wortmannin）抑制胰岛素对3 T3-L1脂肪细胞中葡萄糖转运（GLUT 4从细胞质转移到质膜）的刺激作用。此外，我们分析了在渥曼青霉素和胰岛素存在下GLUT 4的动力学，并得出结论，渥曼青霉素抑制胰岛素对3 T3-L1脂肪细胞中GLUT 4的胞吐的刺激作用，但不抑制胞吞。

项目成果

Kotani, K., Yonezawa, K., Hara, K.et al.: "Involvement of phosphoinositide 3-kinase in insulin or IGF-1-induced membrane ruffling." 13. 2313-2321 (1994)

Kotani, K.、Yonezawa, K.、Hara, K.等人：“磷酸肌醇 3-激酶参与胰岛素或 IGF-1 诱导的膜波动。”

Yonezawa, K., Ando, A., Kaburagi, Y.et al.: "Signal transduction pathways from insulin receptors to Ras : Analysis by mutant insulin receptors." 269. 4634-4640 (1994)

Yonezawa, K.、Ando, A.、Kaburagi, Y.等人：“从胰岛素受体到 Ras 的信号转导途径：通过突变型胰岛素受体进行分析。”

Yonezawa,K.,Ando,A.,Kaburagi,Y.,et al.: "Signal transduction pathways from insulin receptors to Ras:Analysis by mutant insulin receptors." J.Biol.Chem.269. 4634-4640 (1994)

Yonezawa,K.、Ando,A.、Kaburagi,Y. 等人：“从胰岛素受体到 Ras 的信号转导途径：通过突变型胰岛素受体进行分析。”

Dhand,R.: "PI3-kinase:Structure and functional analysis of intersubunit interactions." EMBO J.13. 511-521 (1994)

Dhand, R.：“PI3 激酶：亚基间相互作用的结构和功能分析。”

Clarke,J.F.,Young,P.W.,Yonezawa,K.,et al.: "Inhibition of translocation of GLUT1 and GLUT4 in 3T3-L1 cells by the PI 3-kinase inhibitor,wortmannin." Biochem.J.300. 631-635 (1994)

Clarke,J.F.,Young,P.W.,Yonezawa,K.,et al.：“PI 3-激酶抑制剂渥曼青霉素对 3T3-L1 细胞中 GLUT1 和 GLUT4 易位的抑制。”