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). Here, SLC2A1 is linked to hereditary elliptocytosis.