New model of type 1 diabetes: RNA editing disruption mimics early stage disease with no involvement of virus  

Key Takeaways

• A new model of type 1 diabetes (T1D) explains the anti-viral response that is a hallmark of T1D without the need for a viral infection.
• The research offers a new view for how T1D may develop, with implications for prevention and treatment strategies.

T1D is an autoimmune disease whereby the immune system attacks and destroys insulin-producing beta cells in the pancreas. A leading model for why T1D develops suggests that the disease is initiated by viral infection, which in genetically susceptible individuals causes an autoimmune attack on beta cells. This is supported by extensive research, for example the identification of an anti-viral response in early stage disease. The implications of this view are vast; for example, it suggests the use of anti-viral therapy for preventing T1D. However, despite decades of searching, a causal virus has not been found.

A study published in Cell Metabolism by researchers at the Hebrew University-Hadassah Medical School, Bar-Ilan University and Vanderbilt University introduces a new model for how T1D may develop, explaining the anti-viral response but with no need for viral infection. The team studied a process called RNA editing. Unlike DNA, which is formed from two strands that coil around one another, RNA is normally single-stranded. In some cases, however, RNA can fold in on itself, forming double-stranded RNA. RNA editing is a crucial process for dismantling these aberrant double-stranded RNA molecules. Because double-stranded RNA is a hallmark of many viruses, if endogenous double-stranded RNA is left intact it can be recognized, mistakenly, by the immune system as an indication of an invading virus and trigger a detrimental immune response.  

Using mouse models and isolated human islets, the researchers found that when RNA editing is defective in pancreatic beta cells, the body mounts a massive inflammatory attack, destroying beta cells and eventually leading to diabetes, with features that strikingly resemble T1D. Moreover, they discovered that high levels of blood glucose boost the inflammatory attack, suggesting a vicious cycle whereby beta cell destruction leads to diabetes, which further drives destructive inflammation. Strikingly, independent work has recently discovered that genetically inherited defects in RNA editing predispose people to multiple auto-inflammatory conditions, including T1D, suggesting relevance to human T1D.

Prof. Yuval Dor who led the research, stated, “Our research presents compelling evidence that disruption of RNA editing within beta cells can trigger an inflammatory response resembling early-stage type 1 diabetes. This offers a new view for how T1D may develop, with implications for prevention and treatment strategies.”

Edited by Miriam Kaplan, PhD

Source: Hebrew University of Jerusalem, Medical Xpress, December 27, 2023; see source article