Concurrently, hyperinsulinemia downregulates miR-21 expression in glomerular endothelial cells, activating the MAPK/ET-1 pathway and inhibiting the PTEN/AKT/eNOS pathway, resulting in increased endothelin-1 production and decreased nitric oxide secretion, which causes vasoconstriction and endothelial dysfunction (22). Here, EDN1 is linked to endothelial dysfunction.