GCLM and Hyperglycemia: Thereby, NRF2 not only upregulates the glutamate-cysteine-ligase catalytic and modifier subunit (GCLC, GCLM) as rate limiting for glutathione synthesis and GSH transporters [57,60], but also increases the expression of the light-chain subunit xCT (especially the 40 kDa isoform) of the ubiquitously expressed and sodium-independent cysteine-glutamate exchange system Xc− (SLC7A11), which critically regulates intracellular glutathione synthesis via CySS uptake in response to oxidative stress (but not hyperglycemia) [59,61].