New Model for How Type 1 Diabetes Develops Proposed by Hebrew University 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.”