In the early stages of T2DM, insulin levels are elevated due to insulin resistance, so it is possible that on-going, sustained elevated intra-islet insulin levels are conducive to α-cell proliferation, especially if α-cell proliferative brakes are dysfunctional, and it is also possible that as glucagon secretion begins to rise that it serves to stimulate α-cell proliferation. This evidence concerns the gene INS and type 2 diabetes mellitus.