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

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

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish
Pages (from-to)150-159
Number of pages10
JournalMolecular Metabolism
Volume16
DOIs
StatePublished - 1 Oct 2018
Externally publishedYes

Keywords

  • Glucose
  • Islets
  • Mitochondria
  • Respirometry

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