Grant: Project Grant

One in 10 adults will have diabetes by 2040. The numbers of beta cells in pancreatic islets is insufficient in individuals with both type 1 and type 2 diabetes. Hence, one therapeutic strategy consists of finding ways to increase beta-cell mass either prior to islet transplantation in type 1 diabetes or in individuals at risk for type 2 diabetes. We have identified a molecular pathway centered on the growth factor HB-EGF that is a potent mediator of beta-cell proliferation. The goal of this research is to determine whether this pathway can be harnessed to expand beta-cell mass. We will pursue three specific objectives. The first objective will be to understand how the HB-EGF pathway contributes to the regulation of beta-cell proliferation. The second objective will be to dissect the action of molecules that negatively affect the HB-EGF pathway. The third objective will be to examine its role in beta cells under physiological (pregnancy) and pathological (high-fat diet) metabolic stress conditions. To complete this study we will make use of the expertise existing in our lab after more than 15 years of beta-cell research as well as specialized platforms in the institute. This project will further our understanding of the control of beta-cell proliferation and open novel avenues for diabetes therapy.