NFkB ACTIVATION AND DIABETES





Tammy M. Bray

College of Health and Human Sciences and LPI, Oregon State University, Corvallis, OR 97331



Although many risk factors can trigger the development of type I diabetes, it is likely that reactive oxygen species (ROS) are involved in beta cell death and disease progression. Development of type 2 diabetes is predominantly genetic predisposed and dietary activated, the pathogenesis of the long term disease outcome is also related to ROS. This presentation will focus on the role of antioxidant defense systems in the susceptibility to type I diabetes and on ROS as cellular messengers that regulate the expression of genes leading to ? cell death. Accumulating evidence indicates that increased antioxidant defense systems reduce the susceptibility to diabetes in animal models or in human study. It is suggested that pancreas-specific ROS productions play a critical role in signaling the cellular autoimmune/inflammatory response by activating the transcription factor, NF?B. Various diabetogenic factors may lead to an increase in ROS production, which activates the redox-sensitive NF?B. This may be the initial event for the expression of cytokines and chemotactic agents involved in the inflammatory response. It is believed that this cascade results in a cyclic amplification of ROS and eventually leads to apoptosis and/or necrosis of beta cells. The specificity of antioxidants to inhibit NF?B activation and the hyperglycemic response emphasizes the importance of selectivity in antioxidant therapy. Our understanding of the cellular and mechanistic role of ROS in the etiology of diabetes will help us lead to the development of better prevention strategies.




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