Oxidative stress: the vulnerable β-cell

Abstract

Antioxidative defence mechanisms of pancreatic beta-cells are particularly weak and can be overwhelmed by redox imbalance arising from overproduction of reactive oxygen and reactive nitrogen species. The consequences of this redox imbalance are lipid peroxidation, oxidation of proteins, DNA damage and interference of reactive species with signal transduction pathways, which contribute significantly to beta-cell dysfunction and death in Type 1 and Type 2 diabetes mellitus. Reactive oxygen species, superoxide radicals (O(2)(*-)), hydrogen peroxide (H(2)O(2)) and, in a final iron-catalysed reaction step, the most reactive and toxic hydroxyl radicals (OH(*)) are produced during both pro-inflammatory cytokine-mediated beta-cell attack in Type 1 diabetes and glucolipotoxicity-mediated beta-cell dysfunction in Type 2 diabetes. In combination with NO(*), which is toxic in itself, as well as through its reaction with the O(2)(*-) and subsequent formation of peroxynitrite, reactive species play a central role in beta-cell death during the deterioration of glucose tolerance in the development of diabetes.