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

哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂已广泛应用于临床胰岛移植，以预防移植排斥反应。最近，mTOR抑制剂也报道诱导各种细胞系的自噬。自噬是细胞分解自身成分的一个重要的稳态过程。然而，其对胰岛的作用尚未完全了解。在这项研究中，我们证明了在体外和体内，雷帕霉素治疗诱导胰岛自噬。此外，添加自噬抑制剂导致更好的移植结果。这些结果表明，雷帕霉素与自噬抑制剂将是一种理想的组合，以防止移植排斥反应，而不诱导自噬。

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.