Antioxidants, NF kappa B activation, and diabetogenesis

Although many risk factors can trigger the development of insulin-dependent diabetes (IDDM), it is likely that reactive oxygen species (ROS) play a ce ntral role in beta-cell death and disease progression. This review will foc us on the role of antioxidant defense systems in the susceptibility to IDDM and on ROS as cellular messengers that regulate the expression of genes le ading to beta-cell death. Accumulating evidence indicates that increased an tioxidant defense systems reduce the susceptibility to IDDM in animal model s or in human study. It is suggested that pancreas-specific ROS productions play a critical role in signaling the cellular autoimmune/inflammatory res ponse by activating the transcription factor, NF kappa B, Various diabetoge nic factors may lead to an increase in ROS production, which activates the redox-sensitive NF kappa B, This may be the initial event for the expressio n of cytokines and chemotactic agents involved in the autoimmune/inflammato ry response. It is believed that this cascade results in a cyclic amplifica tion of ROS and eventually leads to apoptosis and/or necrosis of beta cells , The specificity of antioxidants to inhibit NF kappa B activation and the hyperglycemic response emphasizes the importance of selectivity in antioxid ant therapy. Research in this area will contribute significantly to our und erstanding of the cellular and mechanistic role of ROS in the etiology of I DDM and will lead to the development of better prevention strategies.