January 5, 2024 — A new model for how Type 1 Diabetes (T1D) develops challenges the long-held belief that it is caused by viral infection, according to new research led by Hebrew University of Jerusalem researchers.  

T1D is an autoimmune disease that affects approximately 10 million people worldwide, where the immune system attacks and destroys insulin-producing beta cells in the pancreas. In the absence of insulin, glucose concentration in blood increases, leading to a host of complications. Patients, typically diagnosed in childhood, require life-long treatment with insulin. 

In a new study published in Cell Metabolism, the team studied a process called RNA editing, which acts to dismantle endogenous (having an internal cause or origin) RNA molecules that fold on themselves, forming double-stranded RNA (dsRNA), a characteristic of many viruses. The immune system often recognizes these molecules as an indication of an invading virus and triggers a negative immune response. In a biological model, corroborated with human data, the researchers demonstrated that endogenous dsRNA in beta cells can lead to a diabetogenic immune response, thus identifying a virus-independent mechanism for T1D initiation. 

“Our research presents compelling evidence that disruption of RNA editing within beta cells can trigger an inflammatory response resembling early-stage Type 1 diabetes,” says Prof. Yuval Dor, of Hebrew University’s Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine. “This offers a new perspective on how T1D may develop, with implications for prevention and treatment strategies.”  

The researchers discovered that when RNA editing is defective in pancreatic beta cells, the body mounts a massive inflammatory attack, destroying beta cells that resemble T1D. They also found that high blood glucose levels boost the inflammatory attack, suggesting a vicious cycle whereby beta cell destruction leads to diabetes which further drives destructive inflammation.  

Hebrew University researcher, Dr. Agnes Klochendler added, “Identifying a link between natural double-stranded RNA in beta cells, inflammation, and diabetes offers a new perspective on T1D: a paradigm of “the enemy within,” without external viral infection as the triggering event for this disease.”