title: Reactive oxygen and nitrogen species generation, antioxidant defenses, and β-cell function: a critical role for amino acids.
abstract: 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.
authors.affiliation: School of Biomedical Sciences, Curtin University, PO Box U1987, Perth, Western Australia 6845, Australia. philip.newsholme@curtin.edu.au
authors.forename: P
authors.initials: P
authors.lastname: Newsholme
authors.forename: E
authors.initials: E
authors.lastname: Rebelato
authors.forename: F
authors.initials: F
authors.lastname: Abdulkader
authors.forename: M
authors.initials: M
authors.lastname: Krause
authors.forename: A
authors.initials: A
authors.lastname: Carpinelli
authors.forename: R
authors.initials: R
authors.lastname: Curi
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D000975:Antioxidants; D007328:Insulin; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D005978:Glutathione; D005947:Glucose