Relationship of NADPH Oxidase-1 expression to beta cell dysfunction induced by inflammatory cytokines

• NOX-1 is a key mediator of inflammatory cytokine induced beta cell dysfunction.
• Expression of NOX-1 protein results in beta cell dysfunction.
• Deletion of NOX-1 protein confers protection to inflammatory cytokines.
• Inhibition of NOX-1 is a candidate therapeutic target in diabetes.

Redox stress related loss of beta cell function is a feature of diabetes. Exposure of beta cells and islets to inflammatory mediators elevates reactive oxygen species (ROS) and beta cell dysfunction. Direct molecular manipulation of NADPH oxidase-1 (NOX-1) has identified a key role for NOX-1 in cytokine-induced beta cell dysfunction. Plasmid driven elevation of NOX-1 resulted in elevated ROS, loss of glucose-stimulated-insulin-secretion and increased apoptosis. These outcomes on beta cell function are analogous to cytokine treatment. In contrast, reduction of NOX-1 expression, by shRNA, conferred protection to beta cells and islets from the damaging effects of inflammatory cytokines. Collectively, these data support the therapeutic potential for NOX-1 inhibition in diabetes.