However, if the autophagy capacity is compromised triggered by some kind of pathological factor (genetic polymorphisms/alterations, advanced aging, etc.), cellular stress pathways will be enhanced via ER stress, oxidative stress, islet amyloid polypeptide (IAPP) deposition, inflammation, etc. Eventually it leads to β-cell dysfunction, dedifferentiation, cellular demise, peripheral insulin resistance, T2D will ensue if the dysfunctional/depleted β-cells fail to compensate. This evidence concerns the gene INS and type 2 diabetes mellitus.