Grant: Operating Grant

The secretion of insulin from pancreatic beta cells is deficient in individuals with type 2 diabetes. The normal control of insulin secretion relies on a multitude of signals which converge toward the beta cell. In preliminary experiments we have identified a protein known to play a role in modulating signals inside the cell in other tissues, RGS16, as a potential regulator of insulin secretion. The objective of this research is to understand the role of RGS16 in beta-cell function. To that end we will increase or decrease the levels of RGS16 in beta cells and measure the impact of these manipulations on insulin secretion and other markers of beta-cell function and proliferation. We will pursue three specific objectives. The first objective will be to ascertain the role of RGS16 in the regulation of insulin secretion, both under normal and pathological conditions. The second objective will be to examine its role in beta-cell proliferation under physiological (pregnancy) and pathological (high-fat diet) circumstances of beta-cell mass expansion. The third objective will be to identify the mechanisms whereby RGS16 regulates beta-cell function. For this we will employ novel molecular tools which enable one to measure the recruitment of proteins inside the cells upon activation of proteins located at the cell surface. This project will further our understanding of the control of insulin secretion and help identify novel therapeutic targets for the treatment of type 2 diabetes.