1. Mitochondrial complex I subunit deficiency promotes pancreatic α-cell proliferation.
- Author
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Yu, Xuefei, Arden, Catherine, Berlinguer-Palmini, Rolando, Chen, Chun, Bradshaw, Carla, Smith, Anna LM, Whitehall, Julia, White, Michael, Anderson, Scott, Kattner, Nicole, Shaw, James, Turnbull, Doug, Greaves, Laura C, and Walker, Mark
- Abstract
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. Quadruple immunofluorescence was used to quantify mitochondrial subunit expression (complex I and IV) and cell composition in pancreatic islets from mitochondrial DNA mutator mice (PolgA
mut/mut ) and control C57BL/6 mice at 12 and 44 weeks of age. 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. Complex I deficiency promotes α-cell proliferation and alters islet cell composition. • Decreased islet complex I expression was established in PolgAmut/mut mice at 12 weeks. • Decreased islet complex I expression was associated with increased pancreatic α-cell number in PolgAmut/mut mice at 44 weeks. • Increased α-cell proliferation contributes to the increased α-cell number. [ABSTRACT FROM AUTHOR]- Published
- 2022
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