| First Author | Zhang F | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 1822 |
| PubMed ID | 32286278 | Mgi Jnum | J:287584 |
| Mgi Id | MGI:6406004 | Doi | 10.1038/s41467-020-15529-w |
| Citation | Zhang F, et al. (2020) Obesity-induced overexpression of miR-802 impairs insulin transcription and secretion. Nat Commun 11(1):1822 |
| abstractText | 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 beta cell and primary islets impairs insulin transcription and reduction of Fzd5 in beta cell, which, in turn, impairs Ca(2+) signaling, thereby repressing calcium influx and decreasing insulin secretion. We functionally create a novel network between obesity and beta cell dysfunction via miR-802 regulation. Elucidation of the impact of obesity on microRNA expression can broaden our understanding of pathophysiological development of diabetes. |
