The goal of this study is identify novel mechanisms of immune-mediated β-cell death
and dysfunction such that these mechanisms can be exploited to protect against the
onset and progression of T1D. To achieve this goal, we propose the following aims: 1)
Determine if reduced electrical coupling, altered calcium signaling, and activation of
protein kinase C delta (PKCδ) occur in islets from newly diagnosed and autoantibody
positive donors compared to healthy donors 2) Determine if increased activation of
PKCδ correlates with β-cell apoptosis in islets from newly diagnosed and autoantibody
positive donors compared to healthy donors. The results of this study will identify a
novel role for decreased electrical coupling, altered calcium signaling, and activation of
PKCδ in mediating β-cell death and dysfunction in the pathogenesis of T1D.