通过PGC-1alpha和SIRT1复合体,营养控制葡萄糖稳态
Joseph T Rodgers1, Carlos Lerin, Wilhelm Haas
1Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Nature
|March 4, 2005
概括
Sir2的同类物SIRT1通过去乙化PGC-1alpha来控制快餐期间的肝脏葡萄糖代谢. 这一途径将营养信号,葡萄糖平衡和衰老联系在一起,影响能量平衡和糖尿病研究.
科学领域:
- 代谢调节 代谢调节 代谢调节
- 分子生物学分子生物学
- 衰老的研究研究.
背景情况:
- 哺乳动物的恒温机制保持狭窄的血糖范围.
- 卡路里限制会影响葡萄糖代谢和寿命,但与衰老的联系尚不清楚.
研究的目的:
- 阐明SIRT1在葡萄糖代谢中的作用及其与衰老的联系.
- 为了确定链接SIRT1,PGC-1alpha和禁食信号的分子机制.
主要方法:
- 研究了SIRT1在肝脏葡萄糖生成/葡萄糖溶解途径中的作用.
- 检查了SIRT1相互作用和PGC-1alpha脱乙烯化,以应对禁食和pyruvate.
- 分析了葡萄糖生成,甘油和线粒体通路的基因调节.
主要成果:
- 在禁食期间,SIRT1蛋白通过pyruvate信号传递在肝脏中被诱导.
- 在依赖NAD的方式中,SIRT1脱乙PGC-1alpha.
- SIRT1调节PGC-1alpha以诱导葡萄糖生成基因和肝脏葡萄糖输出,并抑制糖性基因.
结论:
- 在葡萄糖恒温中,SIRT1充当PGC-1α的分子调节器.
- 这个机制连接营养信号,能量平衡和衰老.
- 这些发现对了解糖尿病和寿命有意义.
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