As the mechanisms for the stimulation of insulin secretion by GIP and GLP-1 are very similar and mainly involve the generation of cAMP through effects on G proteins coupled to the binding of ligands to GIP and GLP-1 receptors [60], a marked reduction in insulinotropic activity by GIP but widely preserved activity by GLP-1 in type 2 diabetes is surprising and not easily explained. This evidence concerns the gene GIP and type 2 diabetes mellitus.