Adiponectin inhibits the generation of reactive oxygen species induced by high glucose and promotes endothelial NO synthase formation in human mesangial cells.

The aim of this study was to investigate the effects of adiponectin (ADPN) on high glucose (HG)-induced reactive oxygen species (ROS) and the formation of endothelial nitric oxide (NO) synthase (eNOS) in human glomerular mesangial cells (HMCs), as well as to determine which signaling pathways are modulated by ADPN and the mechanisms involved. HMCs cultured in vitro were randomly divided into 4 groups: the control, HG, HG + globular adiponectin (gAd) and HG + gAd + adenine arabinoside (AraA). The generation of ROS was detected using a fluorescent probe. The mRNA expression and protein levels of eNOS were measured by RT-PCR and western blot analysis, respectively. The phosphorylation of AMP-activated protein kinase (AMPK) was assessed by western blot analysis. HMCs treated with ADPN revealed the time-dependent phosphorylation of AMPK. The treatment of HMCs with HG resulted in increased release of ROS and decreased expression of eNOS compared to the control group (p<0.05). Cells treated with ADPN showed a decrease in HG-induced ROS (p<0.05) and an upregulated eNOS expression. The effects of gAd were partly blocked by the AMPK inhibitor, AraA. The results from the present study show that ADPN inhibits the generation of HG-induced ROS in HMCs; it also stimulates eNOS activity, which has a protective effect. The mechanism partly occurs through the stimulation of the AMPK signaling pathway.