Role of nuclear factor (erythroid-derived 2)-like 2 in metabolic homeostasis and insulin action: A novel opportunity for diabetes treatment?

Abstract

Redox balance is fundamentally important for physiological homeostasis. Pathological factors that disturb this dedicated balance may result in oxidative stress, leading to the development or aggravation of a variety of diseases, including diabetes mellitus, cardiovascular diseases, metabolic syndrome as well as inflammation, aging and cancer. Thus, the capacity of endogenous free radical clearance can be of patho-physiological importance; in this regard, the major reactive oxygen species defense machinery, the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) system needs to be precisely modulated in response to pathological alterations. While oxidative stress is among the early events that lead to the development of insulin resistance, the activation of Nrf2 scavenging capacity leads to insulin sensitization. Furthermore, Nrf2 is evidently involved in regulating lipid metabolism. Here we summarize recent findings that link the Nrf2 system to metabolic homeostasis and insulin action and present our view that Nrf2 may serve as a novel drug target for diabetes and its complications.

Vigorous-Intensity Physical Activity is Associated with Metabolic Syndrome Among the Chinese Middle-Aged Population: A Cross-Sectional Study

“…It has been reported that PA can lower blood pressure (Eriksson et al, 1997;Miller et al, 2002), increase insulin sensitivity, decrease abdominal fat (Burstein et al, 1985;Olsen et al, 2008), activate the expression of cellular antioxidant systems (Sachdev & Davies, 2008), and induce anti-inflammatory effects (Jansen et al, 2010;Yu et al, 2012). However, these data do not explain the differences between vigorous and moderate PA in reducing risk of MS. Trapp and colleagues reported that high-intensity interval training caused a significant reduction in total body fat compared with low-intensity steady state exercise in young women (Trapp et al, 2008).…”

The Nrf2-antioxidant response element pathway: a target for regulating energy metabolism

“…The relationship between Nrf2 and the insulin signaling pathway becomes important in the context of insulin resistance, which has been recently reviewed by Yu and colleagues [34]. A conundrum exists, however, in the roles that Nrf2 and insulin have in lipid synthesis.…”

Rosmarinic acid modulates the antioxidant status and protects pancreatic tissues from glucolipotoxicity mediated oxidative stress in high-fat diet: streptozotocin-induced diabetic rats.

“…Recently, the antioxidant potential of polyphenols was attributed to its ability to activate Nrf-2, an important cellular defence mechanism to cope with oxidative stress. The role of Nrf-2 in protecting the vascular complications in diabetes has been emerging and is reported to regulate lipid metabolism [9]. Hence, evaluating efficacy of drug candidates like polyphenols in context with Nrf-2 functional status will shed insights upon its antioxidant potential and can offer promising avenues in therapeutic management of DM.…”