After combination with S1PR1-5, S1P mainly activates ERK, SAPK/JNK, p38-MAPK, and ROCK/Rho signaling pathways to regulate the proliferation of islet β cells, promote insulin secretion, reduce the complications of large vessels, and relieve diabetic nephropathy (see Figure 2 for details). Here, S1PR1 is linked to diabetic kidney disease.