This pathological sequence culminates in endothelial dysfunction characterized by eNOS inactivation-mediated vasodilatory impairment, increased vascular permeability through tight junction protein degradation, and RhoA-ROCK pathway-dependent vasoconstriction—all converging to suppress insulin receptor tyrosine phosphorylation and precipitate systemic insulin resistance (Boido et al., 2015; Cat et al., 2018; Kiyooka et al., 2022). The gene discussed is INS; the disease is endothelial dysfunction.