Taken together, our results using two complementary AIS markers, AnkyrinG (Figs. 4A–C, 5C,D) and βIV spectrin (Fig. 6C–E), indicate that increase of methylglyoxal, but not insulin resistance or high glucose alone (Figs. 1, 2), could be the key initiator of AIS shortening during type 2 diabetes. Here, INS is linked to type 2 diabetes mellitus.