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Disrupted RNA editing in beta cells mimics early-stage type 1 diabetes

ABSTRACT: 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 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE245574 | GEO | 2023/11/01

REPOSITORIES: GEO

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