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Tracking Ca2+ dynamics in NOD mouse islets during spontaneous diabetes development

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posted on 2023-05-31, 18:59 authored by Sandra Postić, Johannes Pfabe, Srdjan Sarikas, Barbara Ehall, Thomas Pieber, Dean Korošak, Marjan Slak Rupnik, Ya-Chi Huang

  

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. 

Funding

MSR received grants from the Austrian Science Fund/Fonds zur Förderung der Wissenschaftlichen Forschung (bilateral grants I3562-B27 and I4319-B30). MSR is a principal investigator on a NIH grant (R01DK127236). MSR and DK received financial support from the Slovenian Research Agency (research core funding program P3-0396).

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