REV-ERB in GABAergic neurons controls diurnal hepatic insulin sensitivity

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 () and Zheng Sun ()
Additional contact information
Guolian Ding: Fudan University
Xin Li: Endocrinology and Metabolism, Baylor College of Medicine
Xinguo Hou: Qilu Hospital of Shandong University
Wenjun Zhou: Endocrinology and Metabolism, Baylor College of Medicine
Yingyun Gong: Endocrinology and Metabolism, Baylor College of Medicine
Fuqiang Liu: Qilu Hospital of Shandong University
Yanlin He: Baylor College of Medicine
Jia Song: Qilu Hospital of Shandong University
Jing Wang: Qilu Hospital of Shandong University
Paul Basil: Endocrinology and Metabolism, Baylor College of Medicine
Wenbo Li: Endocrinology and Metabolism, Baylor College of Medicine
Sichong Qian: Endocrinology and Metabolism, Baylor College of Medicine
Pradip Saha: Endocrinology and Metabolism, Baylor College of Medicine
Jinbang Wang: Qilu Hospital of Shandong University
Chen Cui: Qilu Hospital of Shandong University
Tingting Yang: Endocrinology and Metabolism, Baylor College of Medicine
Kexin Zou: Fudan University
Younghun Han: Baylor College of Medicine
Christopher I. Amos: Baylor College of Medicine
Yong Xu: Baylor College of Medicine
Li Chen: Qilu Hospital of Shandong University
Zheng Sun: Endocrinology and Metabolism, Baylor College of Medicine

Nature, 2021, vol. 592, issue 7856, 763-767

Abstract: Abstract 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.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-021-03358-w Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:592:y:2021:i:7856:d:10.1038_s41586-021-03358-w

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-021-03358-w

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().