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

Mol Metab. 2018 Oct:16:150-159. doi: 10.1016/j.molmet.2018.07.003. Epub 2018 Jul 25.

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.

Keywords: Glucose; Islets; Mitochondria; Respirometry.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Animals
  • Cell Respiration / physiology
  • Female
  • Glucose / metabolism
  • High-Throughput Screening Assays / instrumentation
  • High-Throughput Screening Assays / methods*
  • Humans
  • Insulin / metabolism
  • Insulin Secretion / physiology
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Mitochondria / metabolism
  • Pancreas / metabolism*
  • Primary Cell Culture

Substances

  • Insulin
  • Glucose