Oxidative and nitrosative stress in b-cell apoptosis: their contribution to b-cell loss in type 1 diabetes mellitus
REVIEW ARTICLE: Br J Biomed Sci 2009; 66(4); 208-215
KEY WORDS:
Apoptosis
Diabetes mellitus
Nitric Oxide
Oxidative stress
ABSTRACT
The loss of b-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 b-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 b-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.
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