期刊
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
卷 1861, 期 8, 页码 1929-1942出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagen.2017.05.013
关键词
Pancreatic beta-cells; Oxidative stress; Reactive oxygen species; Cytoprotective enzymes; Cytokine toxicity; Glucolipotoxicity; Diabetes
资金
- Commission of the European Union
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.
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