Pr. Mark Walker
United Kingdom
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Day 2 - 6.00PM to 6.30PM

Impact of ageing on pancreatic islet cell composition in the mitochondrial DNA mutator mouse

Mark Walker 1 on behalf of Xuefei Yu 1, Catherine Arden 1, Chun Chen 2, Carla Bradshaw 2, Julia Whitehall 2, Michael White 1, Scott Anderson 1, James Shaw 1, Doug Turnbull 2, & Laura Greaves 2

1 Diabetes Research Group, Institute of Cellular Medicine, Faculty of Medical Science, Newcastle University, Newcastle upon Tyne, UK. 2 Wellcome Trust Mitochondrial Research Group, Institute of Neuroscience, Faculty of Medical Science, Newcastle University, Newcastle upon Tyne, UK.

Introduction: Mitochondrial DNA mutations can cause diabetes, and the accumulation of somatic mitochondrial mutations has been linked with the ageing process. The PolgA mutator mouse is a model of premature ageing. The aim of this study was to explore the relationship between mitochondrial dysfunction and islet cell composition in the PolgA mouse model.Methods: Immunofluorescence was used to study mitochondrial respiratory subunit expression (complex I and IV) and the cell composition in islets. Experiments were conducted on pancreas tissue from PolgA mice and age-matched wild type (WT) mice at 12 (young) and 44 (old) weeks of age.

Results: Complex I expression was decreased (P<0.001) in islets from young PolgA mice versus young WT mice. However, there were no differences in islet size and cell composition between young PolgA and young WT mice. Comparing old PolgA mice versus old WT mice, complex I expression was lower (P<0.001) and complex IV expression higher (P<0.001) in islets from the old PolgA mice. Alpha cell number per islet was increased in the old PolgA versus old WT mice (P<0.05), but beta-cell number was comparable between the two groups. Ki67 expression is a marker of cell proliferation. The percentage of islets with 1 or more Ki67 positive alpha cells was higher for the old PolgA versus old WT mice (p<0.05).

Conclusions: Complex I deficiency was already present in the islets of young PolgA mice and persisted with age. This was associated with an increase in alpha cell proliferation and number in old PolgA mouse islets. We conclude that altered islet cell composition is part of the premature ageing phenotype in the PolgA mouse.

Short biography

Mark Walker MD is Professor and Honorary Consultant Physician at Newcastle University and Newcastle Hospitals NHS Foundation Trust, UK.  He is Director of the Newcastle NIHR Clinical Research Facility for translational research and was chair of the EASD Scientific Programme Committee from 2010-13. His research interests include the genetic basis of type 2 diabetes, mechanisms of insulin resistance, and mitochondrial diabetes.