Nature:华人团队揭示胰岛素敏感性的昼夜节律调控机制
创作:楸楸 审核:周旸 04月01日
  • 在下丘脑视交叉上核区(SCN),核受体REV-ERB节律性调控基因表达,使得GABA神经元的激活呈现节律性;
  • 敲除小鼠SCN区GABA神经元中的REV-ERB,会破坏GABA神经元的昼夜节律、降低肝脏对胰岛素的敏感性,在觉醒时显著降低糖耐量,但该现象不受进食和运动的影响;
  • II型糖尿病糖尿病患者在黎明时分、早餐后出现高血糖被称为黎明现象,有黎明现象和无黎明现象患者的REV-ERB表达节律存在显著差异,REV-ERB节律异常或可解释黎明现象。
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周旸
正常人体中,肝脏对于胰岛素的敏感性存在昼夜差异,肝脏生糖在觉醒前后达高峰。复旦大学附属妇产科医院丁国莲课题组与美国贝勒医学院孙正课题组、山东大学齐鲁医院陈丽课题组等合作,发现下丘脑视交叉上核区GABA神经元的REV-ERB控制胰岛素抑制肝脏糖异生的昼夜节律。该研究对于深入了解中枢神经系统对外周糖代谢的时空调控具有重要的意义,有助于解释II型糖尿病患者在黎明的血糖异常现象,对于糖尿病患者血糖控制有指导作用。
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Nature [IF:42.778]

REV-ERB in GABAergic neurons controls diurnal hepatic insulin sensitivity

GABA神经元中的REV-ERB基因控制肝胰岛素敏感性的昼夜节律

10.1038/s41586-021-03358-w

03-24, Article

Abstract & Authors:展开

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Systemic insulin sensitivity shows a diurnal rhythm with a peak upon waking1,2. The molecular mechanism that underlies this temporal pattern is unclear. Here we show that the nuclear receptors REV-ERB-α and REV-ERB-β (referred to here as ‘REV-ERB’) in the GABAergic (γ-aminobutyric acid-producing) neurons in the suprachiasmatic nucleus (SCN) (SCNGABA neurons) control the diurnal rhythm of insulin-mediated suppression of hepatic glucose production in mice, without affecting diurnal eating or locomotor behaviours during regular light–dark cycles. REV-ERB regulates the rhythmic expression of genes that are involved in neurotransmission in the SCN, and modulates the oscillatory firing activity of SCNGABA neurons. Chemogenetic stimulation of SCNGABA neurons at waking leads to glucose intolerance, whereas restoration of the temporal pattern of either SCNGABA neuron firing or REV-ERB expression rescues the time-dependent glucose metabolic phenotype caused by REV-ERB depletion. In individuals with diabetes, an increased level of blood glucose after waking is a defining feature of the ‘extended dawn phenomenon’3,4. Patients with type 2 diabetes with the extended dawn phenomenon exhibit a differential temporal pattern of expression of REV-ERB genes compared to patients with type 2 diabetes who do not have the extended dawn phenomenon. These findings provide mechanistic insights into how the central circadian clock regulates the diurnal rhythm of hepatic insulin sensitivity, with implications for our understanding of the extended dawn phenomenon in type 2 diabetes.

First Authors:
Guolian Ding,Xin Li,Xinguo Hou,Wenjun Zhou

Correspondence Authors:
Li Chen,Zheng Sun

All Authors:
Guolian Ding,Xin Li,Xinguo Hou,Wenjun Zhou,Yingyun Gong,Fuqiang Liu,Yanlin He,Jia Song,Jing Wang,Paul Basil,Wenbo Li,Sichong Qian,Pradip Saha,Jinbang Wang,Chen Cui,Tingting Yang,Kexin Zou,Younghun Han,Christopher I Amos,Yong Xu,Li Chen,Zheng Sun

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Nature:视交叉上核(SCN)的REV-ERB控制昼夜肝胰岛素敏感性

2021-04-02

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