组织素脱乙酶Sirt6通过Hif1alpha调节葡萄糖稳态
Lei Zhong1, Agustina D'Urso, Debra Toiber
1The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Cell
|February 10, 2010
概括
这项研究显示,SIRT6蛋白通过调节糖溶性基因来控制葡萄糖水平. 缺少SIRT6会导致低血糖症,影响葡萄糖平衡和代谢性疾病治疗.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- SIRT6是一种依赖NAD (((+) 的脱乙酶,参与新陈代谢和抗压力.
- 缺少SIRT6的小鼠表现出致命的低血糖症,但根本的机制尚不清楚.
研究的目的:
- 为了阐明SIRT6在葡萄糖平衡中的作用.
- 调查SIRT6缺乏导致低血糖的机制.
主要方法:
- 基因素脱乙酶试验. 基因素脱乙酶试验.
- 基因表达分析.
- 在SIRT6缺乏细胞和小鼠中分析细胞葡萄糖吸收和新陈代谢.
主要成果:
- 赛尔特6作为一个基因素H3K9脱乙酶,调节糖溶性基因表达.
- SIRT6作为低氧诱导因子1-alpha (Hif1alpha) 的核心抑制剂.
- 缺少SIRT6导致Hif1alpha活性增加,糖分分解增强,葡萄糖吸收增加,线粒体呼吸减少.
结论:
- SIRT6是葡萄糖平衡的关键调节者,通过其控制甘油性基因表达.
- 在调节Hif1alpha和糖解方面SIRT6的作用为糖尿病和肥胖等代谢疾病提供了潜在的治疗点.
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