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

Udi Ehud Knebel, Shani Peleg, Chunhua Dai, Roni Cohen-Fultheim, Sara Jonsson, Karin Poznyak, Maya Israeli, Liza Zamashanski, Benjamin Glaser, Erez Y. Levanon, Alvin C. Powers, Agnes Klochendler*, Yuval Dor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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.

Original languageAmerican English
Pages (from-to)48-61.e6
JournalCell Metabolism
Issue number1
StatePublished - 2 Jan 2024

Bibliographical note

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  • RNA editing
  • beta cells
  • interferon response
  • islet inflammation
  • metabolic stress
  • type 1 diabetes


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