Oxidative and nitrosative stress in beta-cell apoptosis: their contribution to beta-cell loss in type 1 diabetes mellitus.
The loss of beta-cell mass consequential to the activation of pro-apoptotic signalling events is increasingly recognised as a causal and committed stage in the development of autoimmune, type 1, diabetes mellitus (DM). While the mechanisms responsible for targeted beta-cell loss are multifaceted and difficult to define at a prediabetic stage, there is a need, from a therapeutic perspective, to understand the molecular mechanisms involved. Over recent years the use of animal and cell-line models of DM, together with investigations in isolated ex vivo human islets, have greatly increased our understanding of the processes involved in the pathogenesis of type 1 DM. From this work, several biochemical pathways have emerged that may have future potential for therapeutic intervention. This review looks at the current opinions on the role of apoptosis in beta-cell loss at the molecular level, focusing on a central mechanism for oxidative and nitrosative stress, and suggests biochemical pathways that may have future potential for therapeutic intervention.
Watson
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School of Life Sciences, Huxley Building, Keele University, Staffs ST5 5BG, UK.
Loweth
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AC
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015220:Calcium Channels; D016207:Cytokines / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D004195:Disease Models, Animal; D004579:Electron Transport / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000502:physiology; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D016381:Islets of Langerhans Transplantation; D009569:Nitric Oxide / Q000009:adverse effects; D018384:Oxidative Stress; D051381:Rats; D026361:Reactive Nitrogen Species / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
D015220:Calcium Channels; D016207:Cytokines; D016166:Free Radical Scavengers; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D013482:Superoxide Dismutase