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Metabolic evolution suggests an explanation for the weakness of antioxidant defences in beta-cells

Lookup NU author(s): Armin Rashidi, Emeritus Professor Thomas Kirkwood, Dr Daryl Shanley


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The lack of an effective antioxidant system in beta-cells, which renders them susceptible to oxidative stress, is to date without explanation. The particular weakness of beta-cells in females, in both humans and mice, is another unexplained observation. We hypothesise that reactive oxygen species (ROS) in beta-cells, by their negative effect on insulin synthesis/secretion, play a fitness-enhancing role for the whole organism. Under stress conditions, the release of stress hormones produces insulin resistance and, owing to ROS preventing beta-cells from secreting insulin at the level required to maintain homeostasis, diverts glucose to insulin-independent tissues such as the brain and the foetus. We suggest that pancreatic beta-cells lost part of their antioxidant defence in association with brain evolution, and lost even more in females when placental mammals evolved. The unusual antioxidant status of beta-cells may thus be explained as an instance of co-evolution of the brain, cortisol and corticosteroid receptors, and beta-cells in the endocrine pancreas. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Publication metadata

Author(s): Rashidi A, Kirkwood TBL, Shanley DP

Publication type: Article

Publication status: Published

Journal: Mechanisms of Ageing and Development

Year: 2009

Volume: 130

Issue: 4

Pages: 216-221

ISSN (print): 0047-6374

ISSN (electronic): 1872-6216

Publisher: Elsevier Ireland Ltd.


DOI: 10.1016/j.mad.2008.12.007


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Funder referenceFunder name
Biotechnology and Biological Sciences Research Council
BB/C008200/1Biotechnology and Biological Sciences Research Council