In conclusion, the data we obtained, clearly indicate that ENPP1 exerts invitro a direct detrimental effect on the most important tissues forinsulin sensitivity, insulin secretion and, eventually, glucose metabolism.Additional attempts, aimed at better clarify the role of ENPP1 as a pathogenicfactor predisposing to insulin resistance-related abnormalities and type 2 diabetes,are definitively needed. This evidence concerns the gene INS and type 2 diabetes mellitus.