We surmise that the T2D islets (like the CA-Smad3 mouse islets) are susceptible to apoptosis and have the apoptosis machinery activated as a result of constitutively-active TGF-β signaling, evidenced by high levels of pSMAD3 in the T2D human islets and the CA-Smad3 mouse islets. Here, SMAD3 is linked to type 2 diabetes mellitus.