Nutrient metabolism, subcellular redox state and oxidative stress in pancreatic islets and β-cells

Publication date: Available online 18 October 2019Source: Journal of Molecular BiologyAuthor(s): Leticia P. Roma, Jean-Christophe JonasAbstractInsulin-secreting pancreatic β-cells play a critical role in blood glucose homeostasis and the development of type 2 diabetes (T2D) in the context of insulin resistance. Based on data obtained at the whole cell level using poorly specific chemical probes, reactive oxygen species (ROS) like superoxide and hydrogen peroxide have been proposed to contribute to the stimulation of insulin secretion by nutrients (positive role) and to the alterations of cell survival and secretory function in T2D (negative role). This raised the controversial hypothesis that any attempt to decrease β-cell oxidative stress and apoptosis in T2D would further impair insulin secretion. Over the last decade, the development of genetically-encoded redox probes that can be targeted to cellular compartments of interest and are specific of redox couples allowed the evaluation of short- and long-term effects of nutrients on β-cell redox changes at the subcellular level. The data indicated that the nutrient regulation of β-cell redox signaling and ROS toxicity is far more complex than previously thought, and that the subcellular compartmentation of these processes cannot be neglected when evaluating the mechanisms of ROS production or the efficacy of antioxidant enzymes and antioxidant drugs under glucolipotoxic conditions and in T2D. In this review, we present wha...
Source: Journal of Molecular Biology - Category: Molecular Biology Source Type: research