Reactive oxygen and nitrogen species generation, antioxidant defenses, and β-cell function: a critical role for amino acids

Growing evidence indicates that the regulation of intracellular reactive oxygen species (ROS) and reactive nitrogen species (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 glucose stimulated insulin secretion (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 (GSH) peroxidase, other less known GSH-based antioxidant systems are expressed in beta cells at higher levels. Herein, we discuss the key mechanisms of ROS/RNS production and their physiological function in pancreatic beta cells. We also hypothesize that specific interactions between RNS and ROS may be the cause of the vulnerabilityof pancreatic beta cells to oxidative damage. In addition, using a hypothetical metabolic model based on the data available in the literature, we emphasize the importance of amino acid availability for GSH synthesis and for the maintenance of beta-cell function and viability during periods of metabolic disturbance before the clinical onset of diabetes. Journal of Endocrinology (2012) 214, 11-20