Although these findings are unable to be directly transported in vivo because intracellular TAGE has not been observed in β-cells in DM patients or model animals, our results suggested the possibility that the induction of β-cell death through the generation of intracellular TAGE may more strongly promote the pathology of DM than insulin resistance and a reduction of insulin secretion [4,7,26,27]. This evidence concerns the gene INS and diabetes mellitus.