H2S-related pathomechanisms of diabetic endothelial dysfunction. Left side: Vascular production of H2S in normal blood vessels is largely due to the physiological activity of CSE and MST. Right side: When endothelial cells are placed in elevated extracellular glucose, they respond with increased ROS production (from the mitochondrial electron transport chain, and other sources, not shown). The increased ROS inhibits the MST pathway and (directly and indirectly) enhances the consumption of H2S, leading to a H2S-deficient cellular state. This, in turn, creates additional mitochondrial dysfunction, which produces additional ROS in a positive feedback cycle. DHLA, dihydrolipoic acid; AGE, advanved glycation endproducts; PKC, protein kinase C; PARP, poly(ADP-ribose) polymerase; 3-MP, 3-mercaptopyruvate; ROS, reactive oxygen species; RNS, reactive nitrogen species.