2112-P: Sarco/Endoplasmic Reticulum ATPase (SERCA2) Deficiency in the Nonobese Diabetic (NOD) Mouse Accelerates Type 1 Diabetes Development

Recent evidence has implicated pathways intrinsic to the β cell, such as endoplasmic reticulum (ER) stress, as potential triggers of T1D. ER stress is increased by the loss of ER Ca2+, leading to decreased β cell function and increased β cell apoptosis. Maintenance of intraluminal ER Ca2+ stores is primarily regulated by the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2) pump, and we have shown that β cell SERCA2 expression is reduced in islets from mouse models of T1D prior to, and after, disease onset. Thus, we hypothesized that SERCA2-mediated ER Ca2+ dyshomeostasis could be a major contributor to T1D development. To test this, we generated a mouse model haploinsufficient for SERCA2 on the NOD background (NOD-S2+/-). Compared to wild type littermates (NOD-WT), NOD-S2+/- mice had a higher incidence of diabetes (p