Reactive oxygen and nitrogen species generation, antioxidant defenses, and β-cell function: a critical role for amino acids
|dc.identifier.citation||Newsholme, P. and Rebelato, E. and Abdulkader, F. and Krause, M. and Carpinelli, A. and Curi, R. 2012. Reactive oxygen and nitrogen species generation, antioxidant defenses, and β-cell function: a critical role for amino acids. Journal of Endocrinology. 214: pp. 11-20.|
Growing evidence indicates that the regulation of intracellular reactive oxygen species (ROS) and reactive nitrogen species (RNS) levels is essential for maintaining normal β-cell glucose responsiveness. While long-term exposure to high glucose induces oxidative stress in β 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 β 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 β cells at higher levels. Herein, we discuss the key mechanisms of ROS/RNS production and their physiological function in pancreatic β cells. We also hypothesize that specific interactions between RNS and ROS may be the cause of the vulnerability of pancreatic β 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 β-cell function and viability during periods of metabolic disturbance before the clinical onset of diabetes.
|dc.title||Reactive oxygen and nitrogen species generation, antioxidant defenses, and β-cell function: a critical role for amino acids|
|dcterms.source.title||Journal of Endocrinology|
|curtin.accessStatus||Open access via publisher|