A novel strategy to minimize mTOR-induced autophagy to pancreatic islet beta cells

一种最小化 mTOR 诱导的胰岛 β 细胞自噬的新策略

• 批准号: 20591524
• 负责人: ITO Toshinori
• 金额: $ 3万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-20591524/
• 关键词: 膵島移植; 1型糖尿病; オートファジー; 長期成績; mTOR阻害剤; 3-MA; I型糖尿病; オートファージ; mTOR inhibitor r; mTOR inhibitor

Mammalian target of rapamycin (mTOR) inhibitor has extensively used in clinical islet transplantation to prevent the graft rejection. Recently, mTOR inhibitor has also reported to induce autophagy to various kinds of cell lines. Autophagy is an essential, homeostatic process by which cells break down their own components. However, its role on pancreatic islets has not been thoroughly understood. In this study we demonstrated that both in vitro and in vivo, rapamycin treatment induced autophagy to islets. Furthermore, addition of autophagy inhibitor resulted in better graft outcome. These results suggest that rapamycin with autophagy inhibitor would be an ideal combination to prevent graft rejection without autophagy induction.

雷帕霉素（MTOR）抑制剂的哺乳动物靶标已广泛用于临床胰岛移植以防止移植排斥。最近，MTOR抑制剂还报告诱导自噬对各种细胞系。自噬是一个必不可少的稳态过程，细胞通过其分解自己的组件。但是，它在胰岛上的作用尚未得到充分理解。在这项研究中，我们证明了体外和体内，雷帕霉素处理都将自噬引起胰岛的自噬。此外，添加自噬抑制剂会带来更好的接枝效果。这些结果表明，具有自噬抑制剂的雷帕霉素将是防止移植物排斥而无需自噬诱导的理想组合。

项目成果

異種膵島移植療法の臨床応用に向けた先端研究

异种胰岛移植治疗临床应用进展研究

• 发表时间: 2009
• 作者: 種村匡弘;伊藤壽記;永野浩昭;出口貴司;町田智彦;小林省吾;丸橋繁;武田裕;北川透;堂野恵三;門田守人;森正樹;土岐祐一郎
• 通讯作者: 土岐祐一郎

Development of beta-cells in the native pancreas after pancreas allo-transplantation in the Spontaneously Diabetic Torii rat.

• DOI: 10.1016/j.jss.2007.03.030
• 发表时间: 2008-04
• 期刊: The Journal of surgical research
• 作者: K. Shimada;Toshinori Ito;M. Tanemura;H. Komoda;Y. Fumimoto;K. Kawamoto;T. Nishida;H. Kaneto;Y. Sawa

Pig cellular FLICE-like Inhibitory Protein (c-FLIP) overexpression in pig xenograft cells induces resistance to human CD8^+ CTL-mediated xenocytotoxicity.

猪异种移植细胞中猪细胞FLICE样抑制蛋白（c-FLIP）的过度表达诱导对人CD8^CTL介导的异种细胞毒性的抵抗。

• 发表时间: 2008
• 期刊: Transplant Proc. 40(2)
• 作者: Tanemura M;Saga A;Kawamoto K;Manabe N;Machida T;Deguchi T;Sawa Y;Nishida T;Ito T.
• 通讯作者: Ito T.

Intra- and extracellular remodeling effectively prevent human CD8+ CTL-mediated xenocytotoxicity by coexpression of membrane-bound human FasL and pig c-FLIPL in pig endothelial cells.

通过在猪内皮细胞中共表达膜结合的人 FasL 和猪 c-FLIPL，细胞内和细胞外重塑可有效防止人 CD8 CTL 介导的异种细胞毒性。

• 发表时间: 2009
• 期刊: Transplant Proc. 41(1)
• 作者: Tanemura M;Saga A;Kawamoto K;Machida T;Deguchi T;Nishida T;Sawa Y;Doki Y;Mori M;Ito T.
• 通讯作者: Ito T.

Rapamycin induces autophagy in islets : Relevance for islets transplantation.

雷帕霉素诱导胰岛自噬：与胰岛移植的相关性。

• 发表时间: 2009
• 期刊: Transplantation Proceedings (In press)
• 作者: Tanemura M;Saga A;Kawamoto K;Machida T;Deguchi T;Nishida T;Sawa Y;Doki Y;Mori M;Ito T.
• 通讯作者: Ito T.