These findings strongly suggest that melatonin regulates insulin and glucose metabolism, and may serve as the reason for reduced hyperglycemia-induced hyperammonemia in HE by modulating signaling pathways (cAMP/PKA/Ca2+/cGMP/PKC/Ca2+ pathway/PLC/DAG/PKC/Ca2+ pathway/ERK), and regulating glucose metabolism by acting on its respective receptors (GLUT/InsR). This evidence concerns the gene INS and hereditary elliptocytosis.