title: Cell oxidant stress delivery and cell dysfunction onset in type 2 diabetes.
abstract: Most known pathways of diabetic complications involve oxidative stress. The mitochondria electron transport chain is a significant source of reactive oxygen species (ROS) in insulin secretory cells, insulin peripheral sensitive cells and endothelial cells. Elevated intracellular glucose level induces tricarboxylic acid cycle electron donor overproduction and mitochondrial proton gradient increase leading to an increase in electron transporter lifetime. Subsequently, the electrons leaked combine with respiratory oxygen (O(2)) resulting in superoxide anion ((•)O(2)(-)) production. Advanced glycation end products derive ROS via interaction with their receptors. Elevated diacylglycerol and ROS activate the protein kinase C pathway which, in turn, activates NADPH oxidases. A vicious circle of pathway derived ROS installs. Pathologic pathways induced ROS are activated and persistent though glycemia returns to normal due to hyperglycemia memory. Endothelial nitric oxide synthase may produce both superoxide anion ((•)O(2)(-)) and nitric oxide (NO) leading to peroxynitrite ((•)ONOO(-)) generation. Homocysteine is also implicated in oxidative stress pathogenesis. In this paper we have highlighted the pathologic mechanisms of ROS on atherosclerosis, renal dysfunction, retina dysfunction and nerve dysfunction in type 2 diabetes. Cell oxidant stress delivery have pivotal role in cell dysfunction onset and progression of angiopathies but an early introduction of good glycemic control may protect cells more efficiently than antioxidants.
authors.affiliation: Biochemistry Laboratory, CHU Farhat Hached, Sousse, Tunisia. kassab.asma@laposte.net
authors.forename: Asma
authors.initials: A
authors.lastname: Kassab
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Piwowar
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species