GCLM and type 2 diabetes mellitus: This degradation pathway likely targets NRF2 in the nucleus, and hence impacts the regulation of key stress response genes, in particular Nqo1 and Gclm. In type 2 diabetes, a chronic progressive disease, defects in this pathway would impair beta cell defences against nutrient and inflammatory stress, worsening decline in the functional beta cell mass and accelerating progression toward the need for insulin treatment.