克雷布联合激活剂CRTC2将肝脏ER压力和禁食葡萄糖生成联系在一起
Yiguo Wang1, Liliana Vera, Wolfgang H Fischer
1Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature
|June 23, 2009
概括
克雷布调控转录协激活剂2 (CRTC2) 作为一个双重传感器,对禁食和内分泌网膜 (ER) 应激作用. 通过ATF6alpha,ER压力可以减少肝脏的葡萄糖输出,从而影响葡萄糖平衡.
科学领域:
- 代谢过程中的代谢.
- 细胞生物学 细胞生物学
- 内分泌学 在内分泌学.
背景情况:
- 在禁食哺乳动物中,胰腺葡萄糖激素通过CRTC2刺激肝脏葡萄糖生成.
- 肥胖与肝脏葡萄糖产量增加和内质网膜 (ER) 压力有关,有助于胰岛素抵抗.
研究的目的:
- 调查ER压力是否直接调节葡萄糖生成程序.
- 阐明CRTC2作为ER压力和禁食信号传感器的作用.
主要方法:
- 研究了CRTC2和ATF6alpha在ER应激反应中的相互作用.
- 在肥胖小鼠中利用RNA干扰 (RNAi) 介导的ATF6alpha击退.
- 研究了ATF6alpha过度表达对肝脏葡萄糖输出的影响和葡萄糖生成计划.
主要成果:
- ER应激会诱导CRTC2的脱化和核进入,通过ATF6alpha促进ER质量控制基因表达.
- ATF6alpha 破坏了 CREB-CRTC2 相互作用,抑制了 CRTC2 在糖原基因上的占用,并减少了肝脏的葡萄糖输出.
- 降低肝脏ATF6alpha水平或在肥胖中持续的ER压力可以提高肝脏葡萄糖的输出.
结论:
- CRTC2作为ER压力和禁食信号的双传感器.
- 通过CRTC2和ATF6alpha调节的ER压力和禁食通路之间的交叉交谈对于调节肝脏葡萄糖生产和维持葡萄糖平衡至关重要.
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