title: Metabolic evolution suggests an explanation for the weakness of antioxidant  defences in beta-cells.
abstract: 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.
authors.affiliation: Centre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK. armin.rashidi@newcastle.ac.uk
authors.forename: Armin
authors.initials: A
authors.lastname: Rashidi
authors.forename: Thomas B L
authors.initials: TB
authors.lastname: Kirkwood
authors.forename: Daryl P
authors.initials: DP
authors.lastname: Shanley
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D007328:Insulin; D017382:Reactive Oxygen Species