| First Author | Knebel UE | Year | 2024 |
| Journal | Cell Metab | Volume | 36 |
| Issue | 1 | Pages | 48-61.e6 |
| PubMed ID | 38128529 | Mgi Jnum | J:344303 |
| Mgi Id | MGI:7574023 | Doi | 10.1016/j.cmet.2023.11.011 |
| Citation | Knebel UE, et al. (2024) Disrupted RNA editing in beta cells mimics early-stage type 1 diabetes. Cell Metab 36(1):48-61.e6 |
| abstractText | A major hypothesis for the etiology of type 1 diabetes (T1D) postulates initiation by viral infection, leading to double-stranded RNA (dsRNA)-mediated interferon response and inflammation; however, a causal virus has not been identified. Here, we use a mouse model, corroborated with human islet data, to demonstrate that endogenous dsRNA in beta cells can lead to a diabetogenic immune response, thus identifying a virus-independent mechanism for T1D initiation. We found that disruption of the RNA editing enzyme adenosine deaminases acting on RNA (ADAR) in beta cells triggers a massive interferon response, islet inflammation, and beta cell failure and destruction, with features bearing striking similarity to early-stage human T1D. Glycolysis via calcium enhances the interferon response, suggesting an actionable vicious cycle of inflammation and increased beta cell workload. |
