It has been shown that reactive oxygen species (ROS) are produced in various tissues under diabetic conditions, by the several mechanisms, such as non-enzymatic glycosylation reactions, electron transport chain in the mitochondria and membrane-bound nicotinamide adenine dinucleotide phosphate (NADPH) oxidase [
13]. Several lines of evidence support a close association between oxidative stress and diabetes evolution, revealing that oxidative stress secondary to hyperglycaemia and hyperlipidaemia occurs before the appearance of clinical manifestations of late diabetes complications, suggesting a key role in the pathogenesis of the disease. Therefore, insulin resistance and pancreatic β-cell dysfunction, which are hallmarks of type 2 diabetes, are modulated by ROS [
14‐
16]. Under diabetic condition, chronic hyperglycaemia may induce large amounts of ROS that are responsible for the progressive dysfunction of β cells, worsening insulin resistance and further promoting relative insulin deficiency ROS [
17]. It was previously reported that ROS disrupt insulin-induced cellular redistribution of insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI3K), thus impairing insulin-induced glucose transporter type 4 (GLUT4) translocation in 3T3-L1 adipocytes [
14]. The increase of intracellular free fatty acids (FFA), in turn, leads to a decreased translocation of the glucose transporter subtype 4 (GLUT4) to the plasma membrane, leading to insulin resistance in muscle and adipose tissue [
18]. In this context, insulin resistance may be considered a compensatory mechanism that protects the cells against further insulin-stimulated glucose and fatty acid uptake and, therefore, oxidative damage. Many studies have previously suggested that ß-cell dysfunction results from prolonged exposure to high glucose and FFA levels, or a combination of both [
14,
15]. Beta cells, in particular, are particularly sensitive to ROS because they are low in free-radical quenching (antioxidant) enzymes such as catalase, glutathione peroxidase, and superoxide dismutase [
19,
20]. The ROS formed will also indirectly damage cells by activating a variety of stress-sensitive intracellular signaling pathways, including Nuclear factor-kB (NF-kB), mitogen-activated protein kinase p38 (p38MAPK), kinases JunNH2- terminal/kinases of proteins activated by stress (JNK/SAPK), hexosamines, protein kinase C (PKC) and polyol pathway [
15,
21,
22]. The activation of these cellular signaling cascades is linked not only with the development of diabetic complications but also with the insulin resistance and pancreatic β cell dysfunction. Among the signaling cascades, the NF-kB pathway plays a central role as intermediary of immune and inflammatory responses. This nuclear factor is responsible for regulating the expression of a large number of genes, including those related to diabetes complications, such as the vascular endothelial growth factor (VEGF) [
20]. Being an intracellular signaling pathway target of hyperglycaemia and ROS, its activation may also be induced by endogenous and exogenous stimuli, in addition to those above mentioned, such as excess of FFA, tumour necrosis factor α (TNF-α), interleukin 1β (IL-1β) and other pro-inflammatory cytokines, advanced glycation endproducts (AGE) related to receptor for AGE (RAGE), p38MAPK, DNA damage, viral infection and ultraviolet radiation [
21].