Chemistry and biology of reactive species with special reference to the antioxidative defence status in pancreatic β-cells

Background: Diabetes mellitus is a serious metabolic disease. Dysfunction and subsequent loss of the beta-cells in the islets of Langerhans through apoptosis ultimately cause a life-threatening insulin deficiency. The underlying reason for the particular vulnerability of the beta-cells is an extraordinary sensitivity to the toxicity of reactive oxygen and nitrogen species (ROS and RNS) due to its low antioxidative defense status. Scope review: This review considers the different aspects of the chemistry and biology of the biologically most important reactive species and their chemico-biological interactions in the beta-cell toxicity of proinflammatory cytokines in type 1 diabetes and of lipotoxicity in type 2 diabetes development. Major conclusion: The weak antioxidative defense equipment in the different subcellular organelles makes the beta-cells particularly vulnerable and prone to mitochondrial, peroxisomal and ER stress. Looking upon the enzyme deficiencies which are responsible for the low antioxidative defense status of the pancreatic beta-cells it is the lack of enzymatic capacity for H2O2 inactivation at all major subcellular sites.