Role of beta-cell ryanodine receptors in diabetes

Type 2 diabetes, or diabetes mellitus, is a growing epidemic and a major health problem worldwide. In Canada, the prevalence of diabetes in the general population is around five per cent, but rates as high as 40 per cent have been reported for some indigenous groups. Diabetes can cause serious health problems, including kidney failure, heart disease, stroke and blindness – costing Canada’s health system more than $13 billion annually. It is known that diabetes results from a progressive loss of functional insulin-releasing pancreatic beta-cells. Research evidence suggests that reduced beta-cell survival may be a critical event in this process. The mechanisms underlying beta-cell death in diabetes remain unresolved, but it is becoming increasingly evident that intracellular calcium signals play a vital role in most known types of cell death. Dr. Dan Luciani is examining the role of the ryanodine receptor (RyR), a calcium handling protein, in the death of pancreatic beta-cells. His recent work with colleagues has demonstrated that the flux through these calcium channels regulates beta-cell survival in culture. Using mouse models, he now intends to determine if defects in RyR signaling may predispose to diabetes by testing what happens to beta-cells’ ability to control blood sugar levels when RyR is missing. These studies will lead to a better understanding of the molecular mechanisms that regulate the function and available mass of insulin secreting beta-cells. Ultimately, this knowledge may lead to novel strategies for the treatment, and eventually cure, of this increasingly prevalent disease.