Prevention of Mitochondrial Oxidative Damage as a Therapeutic Strategy in Diabetes

  1. Katherine Green,
  2. Martin D. Brand and
  3. Michael P. Murphy
  1. From the Medical Research Council Dunn Human Nutrition Unit, Cambridge, U.K
  1. Address correspondence and reprint requests to Dr. Michael P. Murphy, MRC Dunn Human Nutrition Unit, Wellcome Trust/MRC Bldg., Hills Rd., Cambridge CB2 2XY, U.K. E-mail: mpm{at}mrc-dunn.cam.ac.uk

Abstract

Hyperglycemia causes many of the pathological consequences of both type 1 and type 2 diabetes. Much of this damage is suggested to be a consequence of elevated production of reactive oxygen species by the mitochondrial respiratory chain during hyperglycemia. Mitochondrial radical production associated with hyperglycemia will also disrupt glucose-stimulated insulin secretion by pancreatic β-cells, because pancreatic β-cells are particularly susceptible to oxidative damage. Therefore, mitochondrial radical production in response to hyperglycemia contributes to both the progression and pathological complications of diabetes. Consequently, strategies to decrease mitochondrial radical production and oxidative damage may have therapeutic potential. This could be achieved by the use of antioxidants or by decreasing the mitochondrial membrane potential. Here, we outline the background to these strategies and discuss how antioxidants targeted to mitochondria, or selective mitochondrial uncoupling, may be potential therapies for diabetes.

Footnotes

  • M.P.M. is a paid consultant for Antipodean Biotechnology.

    This article is based on a presentation at a symposium. The symposium and the publication of this article were made possible by an unrestricted educational grant from Les Laboratoires Servier.

    • Accepted May 30, 2003.
    • Received March 20, 2003.
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