环素D1-Cdk4控制葡萄糖代谢,独立于细胞周期进展
Yoonjin Lee1, John E Dominy2, Yoon Jong Choi3
11] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA [2] Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA [3] Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Nature
|May 30, 2014
概括
胰岛素使用细胞循环蛋白,如cyclin D1-Cdk4,通过调节PGC-1α乙化和肝脏葡萄糖生产来控制葡萄糖水平,为糖尿病治疗提供了新的途径.
科学领域:
- 代谢调节 代谢调节 代谢调节
- 细胞周期控制细胞周期控制
- 糖尿病研究研究 糖尿病研究
背景情况:
- 胰岛素是葡萄糖平衡的关键;它的失调会导致糖尿病.
- PGC-1α将胰岛素信号与代谢基因表达联系起来.
- GCN5和Sirtuin 1通过乙化调节PGC-1α的活性.
研究的目的:
- 研究细胞循环机制在胰岛素代谢作用中的作用.
- 确定将胰岛素信号与葡萄糖代谢联系起来的分子机制.
- 探索糖尿病的治疗目标.
主要方法:
- 鼠标模型 鼠标模型
- 基于细胞的高通量化学选.
- 生物化学试验用于测量乙化和激酶活性.
主要成果:
- 胰岛素激活环林D1-Cdk4,增加GCN5活性,抑制葡萄糖的产生.
- 一种Cdk4抑制剂可以降低PGC-1α乙化.
- 失去了cyclin D1导致高血糖;它的激活使糖尿病模型中的血糖正常化.
结论:
- 胰岛素利用细胞循环成分 (循环素D1-Cdk4) 调节细胞转移后的细胞中的葡萄糖稳态.
- 这一途径控制PGC-1α乙化和肝脏葡萄糖的产生.
- 准D1-Cdk4循环蛋白为糖尿病管理提供了一种新的策略.
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