Through TGR5 activation, BAs also initiate cAMP and its downstream related signaling pathways, type 2 iodothyronine deiodinase (D2), Ca2+/calcineurin-activated nuclear factor of activated T cell 3 (NFAT 3), proprotein convertases 1/3 (PC 1/3) (Morimoto et al., 2016), or mammalian target of rapamycin (mTOR) (Zhai et al., 2018), which stimulate the secretion of GLP-1 from intestinal L cells, promote insulin secretion (Cao et al., 2016; Lasalle et al., 2017), and improve the pancreatic β-cell function and blood glucose homeostasis, thereby improving T2DM. This evidence concerns the gene GCG and type 2 diabetes mellitus.