S1P played a protective role against insulin resistance by activating insulin signaling pathways such as AKT and AMPK via receptor subtypes S1PR1 and/or S1PR3 (Figure 2, Table 1), and improved mitochondrial function to promote glucose metabolism in cells, implying that S1P is considered as a new target for screening hypoglycemic agents (126). This evidence concerns the gene S1PR3 and Insulin resistance.