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333-LB: Impact of Aging on Mitochondrial Respiratory Chain Expression and Pancreatic Islet Cell Composition by Using a Mitochondrial DNA Mutator Mouse Model

2019; American Diabetes Association; Volume: 68; Issue: Supplement_1 Linguagem: Inglês

10.2337/db19-333-lb

1939-327X

Xuefei Yu, Catherine Arden, Chun Chen, Carla Bradshaw, Julia C. Whitehall, Michael G. White, Scott Anderson, James Shaw, Douglass M. Turnbull, Laura C. Greaves, Mark S. Walker,

Mitochondrial Function and Pathology

Introduction: Age-related cumulative mitochondrial mutations can cause mitochondrial dysfunction. The mitochondrial DNA mutator mouse (PolgAmut/mut) is a model of premature ageing and has been previously shown to develop impaired insulin secretion with age. Methods: Immunofluorescence was used to study mitochondrial respiratory chain protein expression (complex I and IV) and the cell composition in islets. Experiments were conducted on pancreas tissue from PolgAmut/mut mice and age-matched wild type (WT) mice at two ages: 12 weeks (young) and 44 weeks (old). Results: (1) Comparing young WT mice versus old WT mice, there was no difference in islet complex I expression, while islet size and beta cell number increased with age (both P<0.01). (2) Comparing young PolgA mut/mut mice versus young WT mice, complex I expression was significantly lower (P<0.01) in islets from young PolgA mut/mut mice. However, there were no significant differences in islet size and cell composition between young PolgA mut/mut and young WT mice. (3) Comparing old PolgA mut/mut mice versus old WT mice, complex I expression was significantly lower (P<0.01) and complex IV expression was significantly higher (P<0.01) in islets from the old PolgA mut/mut mice. Old PolgA mut/mut islets had a lower beta cell percentage (mean ± SEM; 71.8 ± 4 % vs. 89.3 ± 4% P<0.01) but a higher alpha cell percentage (mean ± SEM; 29.6 ± 4 % vs. 12.5 ± 5%; P<0.01) versus old WT mice (both P<0.01). Conclusions: In PolgA mut/mut mice, complex I deficiency was already present in the islets of young mice and persisted with age. This was associated with a proportional increase in alpha cells and decrease in beta cells in islets from old PolgA mut/mut versus the old WT mice. We conclude that complex I deficiency in PolgA mut/mut mice is linked to altered islet cell composition with increasing age. Disclosure X. Yu: None. C. Arden: None. C. Chen: None. C. Bradshaw: None. J. Whitehall: None. M.G. White: None. S.J. Anderson: None. J.A. Shaw: Advisory Panel; Self; Sanofi. Other Relationship; Self; Novo Nordisk A/S. D. Turnbull: None. L. Greaves: None. M. Walker: None.