| First Author | Wang Z | Year | 2021 |
| Journal | Endocrinology | Volume | 162 |
| Issue | 5 | PubMed ID | 33564883 |
| Mgi Jnum | J:316800 | Mgi Id | MGI:6690796 |
| Doi | 10.1210/endocr/bqab031 | Citation | Wang Z, et al. (2021) microRNA-483 Protects Pancreatic beta-Cells by Targeting ALDH1A3. Endocrinology 162(5) |
| abstractText | Pancreatic beta-cell dysfunction is central to the development and progression of type 2 diabetes. Dysregulation of microRNAs (miRNAs) has been associated with pancreatic islet dysfunction in type 2 diabetes. Previous study has shown that miR-483 is expressed relatively higher in beta-cells than in alpha-cells. To explore the physiological function of miR-483, we generated a beta-cell-specific knockout mouse model of miR-483. Loss of miR-483 enhances high-fat diet-induced hyperglycemia and glucose intolerance by the attenuation of diet-induced insulin release. Intriguingly, mice with miR-483 deletion exhibited loss of beta-cell features, as indicated by elevated expression of aldehyde dehydrogenase family 1, subfamily A3 (Aldh1a3), a marker of beta-cell dedifferentiation. Moreover, Aldh1a3 was validated as a direct target of miR-483 and overexpression of miR-483 repressed Aldh1a3 expression. Genetic ablation of miR-483 also induced alterations in blood lipid profile. Collectively, these data suggest that miR-483 is critical in protecting beta-cell function by repressing the beta-cell disallowed gene Aldh1a3. The dysregulated miR-483 may impair insulin secretion and initiate beta-cell dedifferentiation during the development of type 2 diabetes. |
