Obesity-induced overexpression of miR-802 impairs insulin transcription and secretion

Fangfang Zhang, Dongshen Ma, Wanli Zhao, Danwei Wang, Tingsheng Liu, Yuhong Liu, Yue Yang, Yue Liu, Jinming Mu, Bingbing Li, Yanfeng Zhang, Yi Pan, Changying Guo, Hong Du, Ling Li, Xianghui Fu (), Zhengyu Cao () and Liang Jin ()
Additional contact information
Fangfang Zhang: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province
Dongshen Ma: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province
Wanli Zhao: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University
Danwei Wang: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province
Tingsheng Liu: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province
Yuhong Liu: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province
Yue Yang: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province
Yue Liu: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province
Jinming Mu: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province
Bingbing Li: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province
Yanfeng Zhang: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province
Yi Pan: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province
Changying Guo: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province
Hong Du: Department of Endocrinology, Nanjing Jinling Hospital. 305 Zhongshan East Road
Ling Li: Department of Endocrinology, School of Medicine, Zhongda Hospital, Southeast University, 87 DingJiaQiao Rd, Nanjing
Xianghui Fu: Division of Endocrinology and Metabolism, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy
Zhengyu Cao: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University
Liang Jin: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract B cell dysfunction due to obesity can be associated with alterations in the levels of micro-RNAs (miRNAs). However, the role of miRNAs in these processes remains elusive. Here, we show that miR-802 is increased in the pancreatic islets of obese mouse models and demonstrate that inducible transgenic overexpression of miR-802 in mice causes impaired insulin transcription and secretion. We identify Foxo1 as a transcription factor of miR-802 promoting its transcription, and NeuroD1 and Fzd5 as targets of miR-802-dependent silencing. Repression of NeuroD1 in β cell and primary islets impairs insulin transcription and reduction of Fzd5 in β cell, which, in turn, impairs Ca2+ signaling, thereby repressing calcium influx and decreasing insulin secretion. We functionally create a novel network between obesity and β cell dysfunction via miR-802 regulation. Elucidation of the impact of obesity on microRNA expression can broaden our understanding of pathophysiological development of diabetes.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-15529-w Abstract (text/html)

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:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15529-w

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

DOI: 10.1038/s41467-020-15529-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

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