Nutrition plays an important role in the development and also in the prevention of cancer, cardiovascular diseases, and diabetes. A high-fat diet can induce obesity and metabolic disorders, insulin resistance, dyslipidemia, and hypertension in rodents and in humans [1–3]. High-fat diets (HFD) may induce changes not only in energy metabolism but also in liver, kidney and brain function.
Diabetes mellitus, a well-known endocrine metabolic disorder, is disease characterized by high levels of blood glucose and multiple tissue complications, resulting in nephropathy, neuropathy and retinopathy . Oxidative stress and disrupted redox regulation play an important role in the pathogenesis of diabetes and one of the major complications is renal and, in addition to cerebrovascular and ocular complications [5–8]. The production of tumor necrosis factor (TNF)-α and expression of nuclear transcription factor kappa B (NFκB) can be stimulated by over production of reactive oxygen species (ROS) . Inflammatory proteins may also participate in the pathogenesis of insulin resistance and its complications  and therefore, mechanisms by which insulin resistance occurs are explained by excessive activities in the NFκB pathway and of inflammatory cytokines [11–13]. Activated the inhibitor of NF-κB kinase (IKK), caused by cytokines, hyperglycemia and elevated free fatty acids (FFAs), results in the nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) polyubiquitination and proteosomal degradation, and subsequent release of NFκB, especially p50/p65, to the nucleus where it can bind to the response element of target genes involved in the inflammatory response [14–16]. In return sustained activation of NFκB caused by overexpression of IKK in the liver leads to insulin resistance .
Some strategies to alleviate insulin resistance by nutritional supplements appear to improve insulin sensitivity in many individuals and improve glycemic control in diabetics . Chromium (Cr) is required for normal carbohydrate, protein and lipid metabolism and its deficiency has been implicated as one of the causes of diabetes mellitus [18–20]. Supplementations of available Cr chelates with picolinic acid (CrPic) [21, 22] and histidinate (CrHis)  have been shown to exert beneficial effects for the management of type-2 diabetes, as reflected by a decline in insulin response.
Several studies reported that CrPic and CrHis may enhance insulin receptor binding , increase the number of insulin receptors  and insulin receptor phosphorylation , resulting in the reduction of insulin resistance in peripheral tissues . One of the intracellular proteins influencing the insulin receptor is the oligopeptide low molecular weight chromium binding substance (LMWCr, apochromodulin) which is widely distributed in the liver, kidneys, spleen, intestine, testicles and brain [28, 29]. This peptide, which activates tyrosine kinase, depends on Cr concentration and promotes insulin receptor activity.
Although numerous studies have been published examining the health aspects of chromium on humans and animals, there have been scarce studies to investigate the effects of CrHis on the IκB/NF-κB pathway or Nrf2 response in diabetic nephropathy. Therefore, the current study was performed to investigate the effect of CrHis/CrPic supplementation on changes in IκB/NF-κB pathway and Nrf2 levels in the diabetic nephropathy.