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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 | Liang Jin
Nature communications | 2020

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.

Pubmed ID: 32286278

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