林28/let-7轴调节葡萄糖的新陈代谢
Hao Zhu1, Ng Shyh-Chang, Ayellet V Segrè
1Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, MA, USA.
Cell
|October 4, 2011
概括
林28/let-7通路意外地调节了新陈代谢. 林28a/b过度表达会改善胰岛素敏感性和糖尿病抗性,而let-7过度表达会导致胰岛素抗性.
科学领域:
- 分子生物学分子生物学
- 代谢调节 代谢调节 代谢调节
- 遗传学 是一个遗传学.
背景情况:
- Let-7微RNA家族通过调节瘤基因,作为瘤抑制剂.
- RNA结合蛋白 Lin28a/b 抑制了 let-7 的生物发生,促进了癌症.
- 在此之前,Lin28/let-7途径在新陈代谢中的作用是未知的.
研究的目的:
- 研究Lin28/let-7通路在哺乳动物葡萄糖代谢中的作用.
- 确定Lin28a/b和let-7对胰岛素敏感性和葡萄糖平衡的影响.
主要方法:
- 在小鼠中进行过度表达和绝杀研究.
- 对胰岛素-PI3K-mTOR途径组件的分析.
- 评估葡萄糖耐受性和胰岛素敏感性.
- 人类遗传数据的生物信息分析.
主要成果:
- 在小鼠中,Lin28a/b的过度表达赋予了胰岛素敏感性和对高脂肪饮食引起的糖尿病的抗性.
- 肌肉特定的Lin28a损失或let-7过度表达导致胰岛素耐药性和葡萄糖耐受性受损.
- let-7抑制了胰岛素-PI3K-mTOR通路的关键组成部分 (IGF1R,INSR,IRS2).
- 拉帕米辛治疗消除了Lin28a介导的胰岛素敏感性.
- let-7的目标包括与2型糖尿病和禁食葡萄糖控制相关的SNP基因.
结论:
- 林28/let-7通路是葡萄糖代谢的关键调节者.
- 这一途径通过胰岛素-PI3K-mTOR信号级联影响胰岛素敏感性.
- 在let-7目标中的遗传变异与人类2型糖尿病有关.
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