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The glutathione peroxidase pathway is further regulated by System Xc-, an amino acid antiporter consisting of a disulfide-linked heterodimer of xCT/SLC7A11 and SLC3A2/4F2hc/CD98, and is inhibited by the ferroptosis inducer erastin (4)

Recent research has identified additional pro-oxidant enzymes, including NOXs, which are now known to be powerful ROS producers in DPN (134)

This distinction has real biological consequences: a localized, self-limiting signal and a persistent, body-wide one are not merely different doses of the same thing, and the animal literature on localized IGF-1 expression illustrates why