IREB2 and Hyperinsulinemia: In addition, hyperinsulinemia can upregulate hepatic transferrin receptor 1 (TFR1) via PI3K/AKT/mTOR/IRP2 pathway, causing iron overload damage in rat liver, resulting in iron death and reduced cell viability [51], and we found that whereas high insulin concentration leads to ferroptosis in PGCs, high insulin concentration also activates this signaling pathway, validating the results of previous experiments.