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The molecular mechanisms of ferroptosis in diabetic complications involve multiple proteins, including acyl-CoA synthetase long chain family member 4 (ACSL4), high-mobility group box-1 (HMGB1), hypoxia-inducible factor-1 (HIF-1), heme oxygenase-1 (HO-1), tripartite motif containing 46 (TRIM46), circ-PSEN1, NCOA4 (68), and Nox2, and negative genes, Gpx4 , Nrf2 , xCT , adenosine monophosphate-activated protein kinase, heat shock factor 1 ( HSF1 ), and nutrient-deprivation autophagy factor-1 ( NAF-1 ) (69) ( Figure 2 )

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AKT phosphorylation at Ser473 did not change in cells treated with 1 M of U0126 but dramatically increased when cells were treated with 5 or 10 M of U0126 (Fig