Here we show how long-term in vitro exposure of human islet microtissues to glucotoxic and glucolipotoxic culture can reproducibly induce T2D relevant impairment in β-cell function with increased basal insulin secretion and decreased GSIS, the two hallmarks of β-cell dysfunction in T2D [15,16,17,18]. This evidence concerns the gene INS and type 2 diabetes mellitus.