Source: BioValley

A major hypothesis in the etiology of type 1 diabetes is that it is induced by a viral infection, leading to double-stranded RNA (dsRNA) -mediated interferon response and inflammation; however, researchers have so far been unable to identify a pathogenic virus. in a recent study titled "Disrupted RNA editing in beta cells mimics early-stage type 1 diabetes," published in the international journal Cell Metabolism, Scientists from the Hebrew University Hadassah College of Medicine and other institutions have developed a new paradigm for the early stages of type 1 diabetes through research, revealing a new cause of the disease that is not related to viral infection.

Type 1 diabetes is an autoimmune disease that affects nearly 10 million people worldwide. The body's immune system attacks and disrupts the function of the insulin-producing beta cells in the pancreas. When insulin is lacking, glucose levels in the blood rise, leading to a host of complications, usually diagnosed in childhood. And require lifelong insulin treatment. One of the leading models used to study the development of type 1 diabetes suggests that the disease may be caused by a viral infection that, in genetically predisposed individuals, leads to its own immune attack on beta cells, which may be supported by broad information, such as the ability of researchers to detect an antiviral response in the early stages of the disease.

The implications of this idea are very broad, for example, it suggests the use of antiviral therapy to prevent type 1 diabetes in humans, but despite decades of research, scientists have not yet found the virus that causes it. In this study, the researchers introduced a new model to reveal the pathogenesis of type 1 diabetes and explain the body's antiviral response without the need for viral infection. The researchers studied a process called RNA editing, which disassembles endogenous RNA molecules that fold themselves to form double-stranded RNA. Because double-stranded RNA molecules are markers of many viruses, this molecule is often mistakenly recognized by the immune system as an indicator of an invading virus, while also inducing a harmful immune response.

Scientists propose a new paradigm for the development of type 1 diabetes in humans.

The researchers found that when RNA editing in pancreatic beta cells is missing, the body launches a massive inflammatory attack that destroys the beta cells and eventually leads to diabetes, with characteristics very similar to type 1 diabetes. In addition, they found that high levels of blood glucose enhance the body's inflammatory attack, which reveals the vicious cycle of beta cell destruction that induces diabetes, and further drives destructive inflammation in the body; To the researchers' surprise, recent independent studies have shown that a genetic defect in RNA editing may predispose people to a variety of autoimmune diseases, including type 1 diabetes, suggesting a possible link to actual type 1 diabetes in humans.

"Our study provides compelling evidence that disrupting the RNA editing process in beta cells may induce an inflammatory response similar to that seen in early type 1 diabetes, which may shed new light on the onset of type 1 diabetes and have implications for disease prevention and treatment," said Yuval Dor. The researchers add that identifying the link between natural double-stranded RNA in beta cells, inflammation, and diabetes may provide new insights into the pathogenesis of type 1 diabetes, an "enemy within" paradigm that does not require external viral infection as a trigger for the disease.

Taken together, the results of this study suggest that glycolysis may enhance the body's interferon response through calcium ion signaling, thus revealing an executable vicious cycle of increased inflammation and beta cell load.

Original Source:Udi Ehud Knebel, Shani Peleg, Chunhua Dai, et al. Disrupted RNA editing in beta cells mimics early-stage type 1 diabetes, Cell Metabolism (2023). DOI:10.1016/j.cmet.2023.11.011