A study by the Hebrew University suggests a new model that indicates disrupted RNA editing in pancreatic beta cells could trigger an inflammatory response similar to early-stage type 1 diabetes. This new perspective challenges the long-held belief in viral involvement and has potential implications for treatments and cures.
A recent study by researchers from the Hebrew University-Hadassah Medical School, Bar-Ilan University, and Vanderbilt University has developed a new paradigm for early stages of type 1 diabetes (T1D) and suggested a new etiology that does not involve viral infection.
T1D is an autoimmune disease affecting almost 10 million people worldwide. It involves the immune system attacking and destroying the insulin-producing beta cells in the pancreas. Without insulin, blood glucose levels rise, leading to various complications. Patients, typically diagnosed in childhood, require lifelong insulin treatment. A leading model for the onset of T1D is that the disease is triggered by a viral infection, which causes an autoimmune attack on beta cells in genetically susceptible individuals. Although supported by extensive evidence, such as the identification of an antiviral response in the early stages of the disease, no causal virus has been found despite decades of searching. The implications of this view are enormous; for example, the use of antiviral therapy has been suggested for the prevention of type 1 diabetes. However, no causal virus has been found despite decades of searching.
The study, led by Prof. Yuval Dor, Dr. Agnes Klochendler, and MD/phD students Ehud Knebel and Shani Peleg, presents a novel model for the development of T1D and explains the antiviral response without the need for viral infection.
The team investigated a process called RNA editing, which serves to degrade endogenous RNA molecules that fold onto themselves to form double-stranded RNA. Since double-stranded RNA is a hallmark of many viruses, such molecules can often be mistakenly recognized by the immune system as a sign of an invading virus, triggering a harmful immune response. They found that faulty RNA editing in the pancreatic beta cells triggers a massive inflammatory attack by the body, destroying the beta cells and eventually leading to diabetes, with features strikingly reminiscent of T1D.
Furthermore, they discovered that high blood sugar levels exacerbate the inflammatory surge, indicating a vicious cycle where the destruction of beta cells leads to diabetes, which further drives the destructive inflammation. Remarkably, independent work has recently found that genetically inherited defects in RNA editing predispose individuals to several autoinflammatory diseases, including T1D, suggesting relevance to actual human T1D.
Our research provides compelling evidence that disrupted RNA editing in beta cells can trigger an inflammatory response similar to early-stage type 1 diabetes. This offers a new view of the potential development of type 1 diabetes with implications for prevention and treatment strategies.“
Prof. Yuval Dor, Hebrew University-Hadassah Medical School, Bar-Ilan-University
Dr. Agnes Klochendler added: „The identification of a link between natural double-stranded RNA in beta cells, inflammation, and diabetes opens a new perspective on type 1 diabetes: a paradigm of the ‚inner enemy,‘ in which no external virus infection is required as a triggering event for this disease.“
The Institute for Medical Research Israel-Canada (IMRIC) at the Hebrew University’s medical school is dedicated to groundbreaking biomedical research.
Hebrew University of Jerusalem
Knebel, UE, et al. (2023). Disrupted RNA editing in beta cells resembles early-stage type 1 diabetes. Cell Metabolism. doi.org/10.1016/j.cmet.2023.11.011.