Progressive loss of β-cell mass and function is a key defect in both type 1 (T1D) and type 2 (T2D) diabetes. Islet transplantation has provided a feasible approach for β-cell replacement in T1D but is currently limited by short supply and post-transplant loss of islets. Our research focuses on understanding why β-cells die in T2D and islet grafts. Specifically, our studies aim to identify the mechanisms by which protein aggregates called islet amyloid destroy β-cells. The ultimate goal of our research is to develop new therapies to prevent or slow onset of T2D diabetes and enhance long-term survival of islet grafts.