Interestingly, although both receptors couple to Gs to promote intracellular cAMP signaling for insulin secretion, GIP-induced insulin secretion is diminished or absent in T2D individuals, whereas the insulinotropic effect of GLP-1R agonists is still preserved (Holst et al., 2021, Nauck and Meier, 2016). This evidence concerns the gene INS and type 2 diabetes mellitus.