Tracking Ca²⁺ Dynamics in NOD Mouse Islets During Spontaneous Diabetes Development

The mechanisms accounting for the functional changes of alpha- and beta-cells over the course of type 1 diabetes (T1D) development are largely unknown. Permitted by our established technology of high spatiotemporal resolution imaging of cytosolic Ca2+ ([Ca2+](c)) dynamics on fresh pancreas tissue slices, we tracked the [Ca2+](c) dynamic changes, as the assessment of function, in islet alpha- and beta-cells of female nonobese diabetic (NOD) mice during the development of spontaneous diabetes. We showed that, during the phases of islet inflammation, 8 mmol/L glucose-induced synchronized short [Ca2+](c) events in beta-cells were diminished, whereas long [Ca2+](c) events were gradually more triggerable at substimulatory 4 and 6 mmol/L glucose. In the islet destruction phase, the synchronized short [Ca2+](c) events in a subset of beta-cells resumed at high glucose condition, while the long [Ca2+](c) events were significantly elevated already at substimulatory glucose concentrations. In the alpha-cells, the glucose sensitivity of the [Ca2+](c) events persisted throughout the course of T1D development. At the late islet destruction phase, the alpha-cell [Ca2+](c) events exhibited patterns of synchronicity. Our work has uncovered windows of functional recovery in beta-cells and potential alpha-cells functional synchronization in NOD mice over the course of T1D development.