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Lookup NU author(s): Xuefei Yu, Dr Catherine ArdenORCiD, Dr Rolando Berlinguer PalminiORCiD, Dr Chun ChenORCiD, Carla Bradshaw, Anna Smith, Dr Julia Whitehall, Dr Michael White, Dr Scott Anderson, Dr Nicole Kattner, Professor James Shaw, Emeritus Professor Doug Turnbull, Professor Laura GreavesORCiD, Professor Mark Walker
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2022 The AuthorsObjective: There is strong evidence that mitochondrial DNA mutations and mitochondrial dysfunction play a role in diabetes pathogenesis. The homozygous knock-in mtDNA mutator mouse is a model of premature aging due to the accumulation of mitochondrial DNA mutations. We used this mouse model to investigate the relationship between mitochondrial subunit expression and pancreatic islet cell composition. Methods: Quadruple immunofluorescence was used to quantify mitochondrial subunit expression (complex I and IV) and cell composition in pancreatic islets from mitochondrial DNA mutator mice (PolgAmut/mut) and control C57BL/6 mice at 12 and 44 weeks of age. Results: Mitochondrial complex I subunit expression was decreased in islets from 12 week PolgAmut/mut mice. This complex I deficiency persisted with age and was associated with decreased insulin staining intensity at 44 weeks. Complex I deficiency was greater in α-cells compared with β-cells in islets from 44 week PolgAmut/mut mice. Islet cell composition was normal in 12 week PolgAmut/mut mice, but the β: α cell ratio was decreased in islets from 44 week PolgAmut/mut mice. This was due to an increase in α-cell number linked to an increase in α-cell proliferation. Conclusion: Complex I deficiency promotes α-cell proliferation and alters islet cell composition.
Author(s): Yu X, Arden C, Berlinguer-Palmini R, Chen C, Bradshaw C, Smith AL, Whitehall J, White M, Anderson S, Kattner N, Shaw J, Turnbull D, Greaves LC, Walker M
Publication type: Article
Publication status: Published
Journal: Molecular Metabolism
Year: 2022
Volume: 60
Print publication date: 01/06/2022
Online publication date: 04/04/2022
Acceptance date: 28/03/2022
Date deposited: 03/07/2023
ISSN (electronic): 2212-8778
Publisher: Elsevier GmbH
URL: https://doi.org/10.1016/j.molmet.2022.101489
DOI: 10.1016/j.molmet.2022.101489
PubMed id: 35390502
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