INS and renal fibrosis: ESR1, beyond estrogen metabolism regulation, enhances adipocyte insulin sensitivity via the PPARγ/adiponectin pathway and inhibits TGF-β1-mediated renal fibrosis in diabetic nephropathy.[25,26] AKT1, central to the PI3K–Akt pathway, restores glucose homeostasis by promoting FoxO1 nuclear export, suppressing GSK3β activity, and coordinating hepatic glucose synthesis with muscle uptake.[27]