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On the Surprising Weakness of Pancreatic Beta-Cell Antioxidant Defences: An Evolutionary Perspective

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


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Pancreatic beta-cells are unique among other cells in possessing an extremely weak antioxidant defence system. Furthermore, beta-cell defences against oxidative stress in both mice and humans are weaker in females than in males. These observations need an evolutionary explanation given that oxidative stress in beta-cells has an important contribution to the pathogenesis of type 2 diabetes. It turns out that a satisfactory explanation is feasible only by a systems-level approach to the glucose homeostatic system and beta-cell physiology. The connection between physiology and ecology is particularly important in major transitions in the evolutionary history of beta-cells. We have proposed that beta-cells evolved weak antioxidant protection to allow for reactive oxygen species (ROS) to exert a regulatory function directly linked with reproductive fitness of the organism. By down-regulating insulin synthesis and secretion, ROS in beta-cells cooperate with the stress-induced whole-body insulin resistance to divert glucose from insulin-dependent organs to an important insulin-independent structure: the evolving brain. Mammalian evolution provoked further reduction of beta-cell antioxidant defences in females in order to provide the fetus (through the insulin-independent placenta) with a reliable energy Supply in pregnancy. The stress response has driven, within physiological constraints, the co-evolution of beta-cells, the brain and placenta and shaped their current status. We review the hypothesis and explore its implications.

Publication metadata

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

Editor(s): Pontarotti, P.

Publication type: Conference Proceedings (inc. Abstract)

Publication status: Published

Conference Name: Evolutionary Biology: Concept, Modelling and Application, 12th Evolutionary Biology Meeting

Year of Conference: 2009

Pages: 109-125

ISSN: 0071-3260

Publisher: Springer New York LLC

Library holdings: Search Newcastle University Library for this item

ISBN: 19342845