mTOR 信号通路对于胰岛β细胞功能和存活的调控作用及其机制

Regulation and mechanism of mTOR pathway in β-cell function and survival

mTOR 通路是细胞内主要的营养感受器,对于细胞的增殖、生长及代谢具有重要作用。在细胞内,该通路通过与特定蛋白结合形成蛋白复合物而发挥作用。目前发现在哺乳动物中有两种含 mTOR的蛋白复合物：mTORC1和 mTORC2,两者对 mTOR 通路抑制剂雷帕霉素的敏感性不同,在体内更是发挥着截然不同的作用。雷帕霉素作为免疫抑制剂和抗肿瘤药物在临床中应用广泛,然而长期使用可损害β细胞引起糖耐量异常等代谢紊乱。进一步的转基因小鼠模型和体外试验表明,mTORC1和 mTORC2的活性对于维持胰岛细胞数量及功能十分重要。而其是否参与2型糖尿病发病,及其在β细胞内所介导的具体分子机制是目前该领域研究的热点之一。

mTOR pathway plays a critical role in cell proliferation, growth and metabolism. This pathway is composed of two different large protein complexes, mTORC1 and mTORC2, which have their distinct downstream effects. Its inhibitor, rapamycin, has been proved to cause β-cell damage and glucose intolerance. Furthermore, various transgenic mouse models and ex vivo studies have revealed that mTORC1 and mTORC2 are both essential for maintaining normal β cell mass and function, whereas the underlying molecular mechanism and the relevance of the whole mTOR signaling to pathogenesis of type 2 diabetes remain to be explored and further clarified.