title: [Oxidative stress and its effects on insulin resistance and pancreatic beta-cells dysfunction: relationship with type 2 diabetes mellitus complications].
abstract: Type 2 diabetes mellitus, the most prevalent and serious metabolic disease worldwide, is believed to result from the interaction between genetical and lifestyle factors. In genetically predisposed people, the combination of a hypercaloric ingestion and reduced physical activity is responsible for the appearance of insulin resistance. This state can be overcomed, until a certain point, with increments of insulin secretion (hyperinsulinemia). However, an insufficient compensation leads to a state of glucose intolerance, which can evolve to diabetes, according to actual knowledge. The noxious effects of the hyperglycemia, allied with the possible increase of free fatty acids, are mediated by highly reactive molecules, oxygen and nitrogen free radicals species (ROS and RNS). Recent data suggests that these reactive species are signalling molecules and are involved in the regulation of the cellular function, being its increased production or reduced elimination a cause of oxidative stress. Indeed, those free radicals act directly through oxidative damage on macromolecules (proteins, lipids, DNA) or indirectly, activating single transduction pathways sensible to stress mechanisms. In this review, we will consider the pathways recognized as the more significant in stress mechanisms, namely: NF-kB, JNK/SAPK, p38 MAPK, PKC, AGE/RAGE, hexosamines and poliol. These signalling cascades are believed to be responsible for the insulin resistance and reduced insulin secretion, therefore the use of innocuous antioxidant substances such as vitamin C, E and the a-lipoic acid, is seen as a possible step for type 2 diabetic complications management. We will also discuss acetylsalicylic acid potentialities in the above-mentioned pathologies.
authors.affiliation: Serviço de Fisiologia, Faculdade de Medicina da Universidade do Porto, Porto.
authors.forename: J Pedro
authors.initials: JP
authors.lastname: Lopes
authors.forename: Sílvia M
authors.initials: SM
authors.lastname: Oliveira
authors.forename: J
authors.initials: J
authors.lastname: Soares Fortunato
mesh_terms: D048909:Diabetes Complications / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000502:physiology; D018384:Oxidative Stress; D015398:Signal Transduction