Individual islet respirometry reveals functional diversity within the islet population of mice and human donors
| Autor: | Samuel B. Sereda, Orian S. Shirihai, Patrick McDonald, Melena D. Bellin, Eleni Ritou, Marc Liesa, Linsey Stiles, J. J. Wilhelm, Muhamad Abdullah, Andrew Neilson, Kacey Caradonna, Zachary Swanson, Evan P. Taddeo, Dane M. Wolf |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine endocrine system diseases Physiology Mitochondrion Inbred C57BL Mice Respirometry Functional diversity 0302 clinical medicine Insulin Secretion Insulin education.field_of_study geography.geographical_feature_category Glucose sensitivity Diabetes Middle Aged Islet Mitochondria Cell biology medicine.anatomical_structure Female Islets Pancreas Adult endocrine system lcsh:Internal medicine 1.1 Normal biological development and functioning Cell Respiration Primary Cell Culture Population 030209 endocrinology & metabolism Biology Islets of Langerhans 03 medical and health sciences Underpinning research medicine Animals Humans education lcsh:RC31-1245 Molecular Biology Metabolic and endocrine Aged geography Cell Biology High-Throughput Screening Assays Mice Inbred C57BL Glucose 030104 developmental biology Biochemistry and Cell Biology Function (biology) |
| Zdroj: | Molecular Metabolism, Vol 16, Iss, Pp 150-159 (2018) |
| ISSN: | 2212-8778 |
| Popis: | 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: Islets, Mitochondria, Respirometry, Glucose |
| Databáze: | OpenAIRE |
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