The mechanisms accounting for the functional changes of α- and β-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 α- and β-cells of female non-obese diabetic (NOD) mice along the development of spontaneous diabetes. We showed that during the phases of islet inflammation, 8 mM glucose-induced synchronized short [Ca2+]c events in β-cells were diminished, whereas long [Ca2+]c events were gradually more triggerable at sub-stimulatory 4 and 6 mM glucose. In the islet destruction phase, the synchronized short [Ca2+]c events in a subset of β-cells resumed at high glucose condition, while the long [Ca2+]c events were significantly elevated already at sub-stimulatory glucose concentrations. In the α-cells, the glucose sensitivity of the [Ca2+]c events persisted throughout the course of T1D development. At the late islet destruction phase, the α-cell [Ca2+]c events exhibited patterns of synchronicity. Our work has uncovered windows of functional recovery in β-cells and potential α-cells functional synchronization in NOD mice over the course of T1D development.

中文翻译：

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追踪自发性糖尿病发展过程中 NOD 小鼠胰岛的 Ca2+ 动态

1 型糖尿病 (T1D) 发展过程中 α 和 β 细胞功能变化的机制在很大程度上尚不清楚。在我们已建立的新鲜胰腺组织切片上细胞质 Ca2+ ([Ca2+]c) 动态高时空分辨率成像技术的允许下，我们跟踪了胰岛 α 和 β 细胞中 [Ca2+]c 的动态变化，作为功能评估雌性非肥胖糖尿病（NOD）小鼠自发性糖尿病的发展过程。我们发现，在胰岛炎症阶段，8 mM 葡萄糖诱导的 β 细胞中同步短 [Ca2+]c 事件减少，而在亚刺激 4 和 6 mM 葡萄糖下，长 [Ca2+]c 事件逐渐更容易触发。在胰岛破坏阶段，β细胞子集中同步的短[Ca2+]c事件在高葡萄糖条件下恢复，而长[Ca2+]c事件在亚刺激葡萄糖浓度下已经显着升高。在 α 细胞中，[Ca2+]c 事件的葡萄糖敏感性在整个 T1D 发展过程中持续存在。在胰岛破坏后期，α 细胞 [Ca2+]c 事件表现出同步性模式。我们的工作揭示了 NOD 小鼠在 T1D 发展过程中 β 细胞功能恢复的窗口和潜在的 α 细胞功能同步。