Notably, NF-κB signaling intersects with insulin signaling at multiple levels: it negatively regulates insulin receptor substrate (IRS) activity, thereby fostering insulin resistance, while impaired PI3K/AKT signaling (common in insulin-resistant states) cannot suppress NF-κB activity, creating a vicious cycle of inflammation and metabolic disruption [94,95]. This evidence concerns the gene NFKB1 and Insulin resistance.