Abstract

Growing evidence indicates that the regulation of intracellular ROS and RNS levels is essential for maintaining normal beta-cell glucose responsiveness. While long-term exposure to high glucose induces oxidative stress in beta cells, conflicting results have been published regarding the impact of ROS on acute glucose exposure and their role in GSIS. Although beta cells are considered to be particularly vulnerable to oxidative damage, as they express relatively low levels of some peroxide-metabolizing enzymes such as catalase and glutathione peroxidase, other less known glutathione-based antioxidant systems are expressed in beta cells at higher levels. Herein, we discuss the key mechanisms of ROS/RNS production and their physiologic function in pancreatic beta cells. We also hypothesize that specific interactions between RNS and ROS may be the cause of the vulnerability of pancreatic beta-cells to oxidative damage. In addition, using a hypothetical metabolic model based on the data available in the literature, we have emphasized the importance of amino acid availability for glutathione synthesis and for the maintenance of beta cell function and viability during periods of metabolic disturbance before the clinical onset of diabetes.