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

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Abstract

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 methods for detecting single islet function. 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). 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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Taddeo, E. P., Stiles, L., Sereda, S., Ritou, E., Wolf, D. M., Abdullah, M., … Shirihai, O. S. (2018). Individual islet respirometry reveals functional diversity within the islet population of mice and human donors. Molecular Metabolism, 16, 150–159. https://doi.org/10.1016/j.molmet.2018.07.003

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