In a recent publication in Cell Metabolism, researchers from the Hebrew University-Hadassah Medical School, Bar-Ilan University, and Vanderbilt University have introduced a novel paradigm for the early stages of type 1 diabetes (T1D), challenging the prevailing notion of viral infection as a primary trigger.
T1D, an autoimmune disease affecting nearly 10 million individuals globally, involves the immune system attacking and annihilating insulin-producing beta cells in the pancreas. The absence of insulin leads to elevated blood glucose levels, resulting in various complications. Current treatments for patients diagnosed, often in childhood, require life-long insulin therapy.
The conventional model implicates viral infection as a precursor to T1D, initiating an autoimmune assault on beta cells in genetically predisposed individuals. Despite extensive research, a specific causal virus remains elusive.
Led by Prof. Yuval Dor, Dr. Agnes Klochendler, and MD/Ph.D. students Ehud Knebel and Shani Peleg, the new research proposes an alternative model for T1D development, one that accounts for the observed anti-viral response without invoking viral infection.
The focus of the study was on RNA editing, a process that disassembles endogenous RNA molecules forming double-stranded RNA. Mistakenly recognized by the immune system as a viral indicator, these molecules can trigger an inflammatory response, potentially leading to the destruction of beta cells.
The researchers identified that defective RNA editing in pancreatic beta cells initiates a robust inflammatory attack, mimicking T1D characteristics. Notably, elevated blood glucose levels exacerbate this inflammatory response, establishing a feedback loop where beta cell destruction induces diabetes, further intensifying destructive inflammation.
Significantly, other independent research has linked genetically inherited RNA editing defects to multiple auto-inflammatory conditions, including T1D, underscoring the relevance to human T1D.
Prof. Yuval Dor emphasized, “Our research provides 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 perspective for how T1D may develop, with implications for prevention and treatment strategies.”
Dr. Agnes Klochendler highlighted the importance of identifying a connection between natural double-stranded RNA in beta cells, inflammation, and diabetes, presenting a fresh outlook on T1D—a paradigm of ‘the enemy within' that doesn't necessarily hinge on external viral infection as the disease's initiating event.
Source: Hebrew University of Jerusalem