NOX4 and diabetes mellitus: Importantly, SESN2-dependent AMP-activated protein kinase (AMPK) activation has been reported to attenuate high glucose-induced glomerular mesangial cell fibronectin synthesis through blockade of NADPH oxidase 4 (Nox4)-dependent ROS and peroxynitrite generation, with subsequent endothelial nitric oxide synthase (eNOS) uncoupling (Eid et al. 2013), suggesting a protective function for sestrin-2/AMPK and potential targets for intervention to prevent fibrotic injury in diabetes.