INS and type 2 diabetes mellitus: Furthermore, most recent studies also revealed that Smad3 can transcriptionally suppress islet β cell development and insulin production as Smad3 can directly target Pdx-1, Ins1, Ins2, Nkx6.1, Glp1-R and NeuroD1 12, 13, implying that Smad3 transcriptionally regulates islet β cell proliferation and function to influence the progression and regression of T2D 14.