Growing evidence identifies subtle secretory system defects in pancreatic β-cells during early stages of type-2 diabetes [20,21] and several types of monogenic diabetes linked with malfunctioning β-cell endoplasmic-reticulum (ER) (e.g., neonatal diabetes caused by proinsulin mutations [22], Mature Onset Diabetes of the Young type-4 or MODY4 [23], Wolcott-Rallison syndrome [24], Wolfram syndrome [25]). This evidence concerns the gene INS and diabetes mellitus.