Individual islet respirometry reveals functional diversity within the islet population of mice and human donors

个体胰岛呼吸测定揭示小鼠和人类供体的胰岛群功能多样性

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作者:Evan P Taddeo, Linsey Stiles, Samuel Sereda, Eleni Ritou, Dane M Wolf, Muhamad Abdullah, Zachary Swanson, Josh Wilhelm, Melena Bellin, Patrick McDonald, Kacey Caradonna, Andrew Neilson, Marc Liesa, Orian S Shirihai

Conclusions

We have developed a novel methodology capable of analyzing mitochondrial function in large-sized individual islets. By highlighting islet functional heterogeneity, we hope this methodology can significantly advance islet research.

Methods

We have developed a novel non-invasive, high-throughput methodology capable of assessing mitochondrial respiration in large-sized individual islets using the XF96 analyzer (Agilent Technologies).

Objective

Islets from the same pancreas show remarkable variability in glucose sensitivity. While mitochondrial respiration is essential for glucose-stimulated insulin secretion, little is known regarding heterogeneity in mitochondrial function at the individual islet level. This is due in part to a lack of high-throughput and non-invasive

Results

By increasing measurement sensitivity, we have reduced the minimal size of mouse and human islets needed to assess mitochondrial respiration to single large islets of >35,000 μm2 area (∼210 μm diameter). In addition, we have measured heterogeneous glucose-stimulated mitochondrial respiration among individual human and mouse islets from the same pancreas, allowing population analyses of islet mitochondrial function for the first time. Conclusions: We have developed a novel methodology capable of analyzing mitochondrial function in large-sized individual islets. By highlighting islet functional heterogeneity, we hope this methodology can significantly advance islet research.

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