In a rat model of HFD-induced hyperinsulinemia, daily oral administration of caffeic acid (30 mg/kg) for 30 weeks significantly reduced plasma glucose and insulin levels, improved insulin resistance, and upregulated insulin signaling proteins, including the insulin receptor, PI3K, AKT, and insulin-degrading enzymes in the brain [89]. The gene discussed is PIK3CA; the disease is Insulin resistance.