Pharmacy times - Hebrew U researchers suggest New Theory on the Development of Type 1 Diabetes

Defective RNA editing in cells in the pancreas may spur the body to initiate an inflammatory attack against its own cells.

Type 1 diabetes (T1D) may be triggered when the body has an anti-viral response, according to the authors of a recent study conducted by researchers at the Hebrew University-Hadassah Medical School, Bar-Ilan University, and Vanderbilt University. Surprisingly though, no viral infection needs to be present in the body to initiate this response. In effect, researchers theorize that T1D could be a paradigm of ‘the enemy within,’ according to study author Agnes Klochendler, PhD, associate researcher at The Hebrew University of Jerusalem, in a press release.

Approximately 10 million people have T1D globally, according to estimates. T1D is an autoimmune disease that often arises during childhood. In T1D, a person’s immune system destroys beta cells in the pancreas that produce insulin. Insulin is a hormone that allows cells in the body to uptake blood sugars for energy, and without it, blood glucose concentrations rise to dangerous levels.

T1D differs from type 2 diabetes (T2D) in that it is auto-inflammatory. Patients with T2D can develop the disease because of external factors like lifestyle and diet, while the development of T1D is independent of these habits. Currently, patients can manage T1D by taking insulin, although both conditions can require insulin.

Current theories about T1D point to viral infection as the root cause of disease development in people with an associated genetic disposition, however, no one has discovered the virus responsible. Thus, while anti-viral treatment seems like a possible preventative measure, a target virus is necessary to progress treatment development.

Researchers decided to study RNA editing to see if there is a possible non-viral cause of T1D development. During RNA editing, endogenous RNA molecules form double-stranded RNA molecules; many viruses also have double-stranded RNA, so the immune system may attack non-viral RNA because it assumes it is also viral.

Prof. Yuval Dor, Hebrew University of Jerusalem
Prof. Yuval Dor, Hebrew University of Jerusalem

When researchers studied this process in pancreatic beta cells, they observed that the defective RNA editing triggered an inflammatory attack from the body. This inflammatory attack was reminiscent of early-stage T1D, explained Yuval Dor, PhD, professor at The Hebrew University of Jerusalem.

“Our research presents compelling evidence that disruption of RNA editing within beta cells can trigger an inflammatory response resembling early-stage type 1 diabetes,” Dor said in the press release.

During this inflammatory attack, the body destroyed beta cells which caused blood glucose to rise in the body, and in effect this rise in blood sugar can drive inflammation even more, eventually leading to the development of diabetes that resembled T1D.

According to the authors, there has been other research that has shown that defects in RNA editing can be genetic and can predispose people to multiple auto-inflammatory conditions like T1D.

“This [research] offers a new view for how T1D may develop, with implications for prevention and treatment strategies,” Dor said in the press release.