The overall goal of this proposal is to test the hypothesis that β-cell de-differentiation is an early stress-related response that may account for the early loss of β-cells in T1D. Furthermore, we believe that a small but significant population of long-term T1D patients might still have de-differentiated β-cells in their pancreatic islets, which creates hope for future re-differentiation paradigms. The ultimate goal is to address questions whose answers could lead to treatments that prevent β-cell loss and promote re-differentiation of progenitor-like cells into β-cells.