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

Armin Rashidi, T. B L Kirkwood, Daryl P. Shanley

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)216-221
Number of pages6
JournalMechanisms of Ageing and Development
Issue number4
StatePublished - Apr 2009

Bibliographical note

Funding Information:
The work of AR is supported by a Dorothy Hodgkin Postgraduate Award. TBLK and DPS are supported by the BBSRC/EPSRC-funded Centre for Integrated Systems Biology of Ageing and Nutrition (CISBAN). Part of this work was supported by and carried out within the EU-funded Network of Excellence LifeSpan (FP6 036894).

Copyright 2009 Elsevier B.V., All rights reserved.


  • Antioxidant
  • Beta-cell
  • Brain
  • Evolution
  • Insulin resistance
  • Stress


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