Pflügers Archiv - European Journal of Physiology

, Volume 460, Issue 4, pp 703–718 | Cite as

Oxidative stress and beta-cell dysfunction

  • Gisela Drews
  • Peter Krippeit-Drews
  • Martina Düfer
Invited Review

Abstract

Diabetes mellitus type 1 and 2 (T1DM and T2DM) are complex multifactorial diseases. Loss of beta-cell function caused by reduced secretory capacity and enhanced apoptosis is a key event in the pathogenesis of both diabetes types. Oxidative stress induced by reactive oxygen and nitrogen species is critically involved in the impairment of beta-cell function during the development of diabetes. Because of their low antioxidant capacity, beta-cells are extremely sensitive towards oxidative stress. In beta-cells, important targets for an oxidant insult are cell metabolism and KATP channels. The oxidant-evoked alterations of KATP channel activity seem to be critical for oxidant-induced dysfunction because genetic ablation of KATP channels attenuates the effects of oxidative stress on beta-cell function. Besides the effects on metabolism, interference of oxidants with mitochondria induces key events in apoptosis. Consequently, increasing antioxidant defence is a promising strategy to delay beta cell failure in (pre)-diabetic patients or during islet transplantation. Knock-out of KATP channels has beneficial effects on oxidant-induced inhibition of insulin secretion and cell death. Interestingly, these effects can be mimicked by sulfonylureas that have been used in the treatment of T2DM for many years. Loss of functional KATP channels leads to up-regulation of antioxidant enzymes, a process that depends on cytosolic Ca2+. These observations are of great importance for clinical intervention because they show a possibility to protect beta-cells at an early stage before dramatic changes of the secretory capacity and loss of cell mass become manifest and lead to glucose intolerance or even overt diabetes.

Keywords

Sulphonylurea Mitochondria Diabetes mellitus Oxidative stress Apoptosis ATP-dependent potassium channel SUR1 Hydrogen peroxide Transplantation Pancreatic beta-cell 

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Gisela Drews
    • 1
  • Peter Krippeit-Drews
    • 1
  • Martina Düfer
    • 1
  1. 1.Institute of Pharmacy, Department of Pharmacology and Clinical PharmacyUniversity of TübingenTübingenGermany

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