在GABA活性神经元中的REV-ERB控制了白天肝脏的胰岛素敏感性
Guolian Ding1,2,3, Xin Li3, Xinguo Hou4
1Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China.
Nature
|March 25, 2021
概括
大脑中的核受体REV-ERB
科学领域:
- 时间生物学
- 神经内分泌学
- 代谢调节
背景情况:
- 系统性胰岛素敏感性表现出每天的节奏,在醒来时达到顶峰.
- 这种日间模式的基本分子机制仍然很大程度上未知.
- 糖尿病的"延长黎明现象"涉及早晨血糖升高.
研究的目的:
- 阐明胰岛素敏感性日间节律的分子控制.
- 研究REV-ERB核受体在SCNGABAergic神经元中的作用.
- 探索生物钟机制与延长的黎明现象之间的联系.
主要方法:
- 使用小鼠模型研究REV-ERB在上神经核 (SCN) GABAergic神经元中的功能.
- 使用化学遗传学来操纵SCN GABAergic神经元活动.
- 与REV-ERB和SCN神经元活动相关的基因表达模式和葡萄糖代谢.
- 在2型糖尿病患者的REV-ERB基因表达与没有延长的黎明现象进行比较.
主要成果:
- 在SCN GABA活性神经元中,REV-ERB控制肝脏葡萄糖生产的日常节奏.
- REV-ERB调节神经传递基因表达和SCN GABAerg神经元中的发射活动.
- 破坏REV-ERB或SCN神经元的节律性会导致葡萄糖不耐受;恢复节律可以挽救这种表型.
- 在2型糖尿病患者中观察到不同的REV-ERB基因表达模式.
结论:
- 在SCN GABAergic神经元中的REV-ERB核受体是白天胰岛素敏感度节律的关键调节者.
- 这些发现提供了中央昼夜时钟和肝脏葡萄糖调节之间的机制联系.
- 这项研究提供了对2型糖尿病延长黎明现象的见解,表明REV-ERB的作用.
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