Type 1 diabetes (T1D) is a complex disease and the exact reason why it occurs in some people and not others remain unknown. This lack of knowledge regarding the underlying mechanism of T1D development is one of the main reasons why the search for a cure has been so difficult. However, researchers at the Diabetes Research Institute (DRI) have finally uncovered a potentially important pathway in T1D development and have found that when they block this pathway in an experimental model of T1D they can prevent T1D from occurring and in some situations cure established cases of T1D.
Pancreatic beta cells are essential for insulin production and their destruction is a key factor in the development of T1D. Over the years, researchers who work on diabetes have struggled to find effective interventions to halt the deterioration of pancreatic beta cells in individuals with early stage T1D. However, these recent pivotal findings at the DRI may lead to the development of effective strategies to delay or prevent beta cell death.
At the heart of this recent discovery is a molecule that is released by damaged and dying cells in the pancreas and which is produced in high quantities when sugar levels are increased. This molecule (which is called extracellular adenosine triphosphate [eATP]), triggers signals summoning immune cells into the pancreas. The subsequent inflammatory reaction leads to the destruction of pancreatic beta cells. The researchers therefore believe that eATP is acting as a signal to tell the immune system to attack the pancreatic beta cells.
The scientists at DRI used this new information to design novel strategies to block eATP and therefore prevent the immune cells from infiltrating the pancreas and attacking the beta cells. They discovered another protein (CD39) which is normally actively involved in managing eATP levels. When used as a treatment in an experimental model of T1D, soluble CD39 was able to convert eATP into a harmless substance, with an anti-inflammatory and protective effect. The researchers also combined soluble CD39 treatment with another treatment which is under investigation (anti-CD3) and found that this combination therapy had additional protective effects and was able to reverse T1D in experimental models.
Dr Pileggi and colleagues at the DRI published their study in the journal Diabetes on August 25. The manuscript describes the role that eATP signaling plays in the development of T1D and highlights the potential for therapeutic manipulation of eATP signaling in individuals with T1D.
While further research is needed to determine the full implications of these findings, this breakthrough offers renewed hope in the quest to find a cure from T1D.