Indexed on: 12 Mar '17Published on: 06 Mar '17Published in: The Journal of Nutritional Biochemistry
Nrf2 (Nuclear factor erythroid 2-related factor-2) is a transcription factor regulates oxidative/xenobiotic stress response and also suppress inflammation. Nrf2 signaling is associated with an increased susceptibility to various kinds of stress. Nrf2 has shown as a promising therapeutic target in various human diseases including diabetes. Our earlier studies showed that Pterostilbene (PTS) as a potent Nrf2 activator and protect the pancreatic β-cells against oxidative stress. In this study, we investigated PTS confer protection against cytokine stress in MIN6, a pancreatic beta cells, and its role in insulin secretion in streptozotocin (STZ)-induced diabetic mice. The Nrf2 activation potential of PTS was assessed by dissociation of the Nrf2–Keap1 complex and by expression of ARE-driven downstream target genes in MIN6 cells. Further the nuclear Nrf2 translocation and blockage of apoptotic signaling as demonstrated by the reduction of BAX/Bcl-2 ratio, Annexin-V positive cells and caspase-3 activity conferred cyto-protection of PTS against cytokine-induced cellular damage. In addition, PTS treatment markedly improved glucose homeostasis and abated inflammatory response evidenced by reduction of pro-inflammatory cytokines in diabetic mice. The inhibition of β-cell apoptosis by PTS as assessed by BAX/Bcl-2 ratio and caspase-3 activity in the pancreas was associated with activation of Nrf2 and the expression of its downstream target genes. PTS also inhibited the activation of iNOS, and decreased nitric oxide (NO) formation in the pancreas of diabetic animals. The results obtained from both in vitro and in vivo experiments showed that PTS improves β-cell function and survival against cytokine stress and also prevents STZ-induced diabetes.