Grant: Project Grant

One in 10 adults will have diabetes by 2040. Type 2 diabetes (T2D) is by far the predominant form and affects more than 3M Canadians. The root to addressing this major public health challenge will be the identification of the major, druggable molecular players, a prerequisite to the design of more effective therapeutic strategies. The secretion of insulin from the beta cell in pancreatic islets is deficient in individuals with T2D. Hence, one therapeutic strategy consists of finding ways to increase functional beta-cell mass in T2D. We have identified a protein known to play a role in modulating signals inside the cell in other tissues, called RGS16, as a regulator of insulin secretion and beta-cell proliferation. The goal of this research is to elucidate the role and evaluate the benefits of targeting RGS16 in beta cells for the treatment of T2D. We will pursue three specific objectives. The first objective will be to ascertain the mechanism of RGS16 action in the regulation of insulin secretion and beta-cell proliferation. The second objective will be to examine its role in beta cells under physiological (pregnancy) and pathological (high-fat diet) metabolic stress conditions. The third objective will be to assess whether targeting RGS16 to increase its activity in the beta cell is a potential therapeutic strategy for the treatment of T2D. To complete this study we will make use of the expertise existing in our lab after more than 30 years of beta-cell research as well as specialist platforms in the institute. This project will further our understanding of the control of insulin secretion and beta-cell proliferation and open novel avenues for T2D therapy.