Proinsulin maturation disorder is a contributor to the defect of subsequent conversion to insulin in β-cells

► Primary proinsulin maturation disorder is inherent in Ins2+/Akita islets/β-cells. ► A consequence is the inefficient conversion of proinsulin to insulin. ► Post-translational defects occur as well in the involved PC1/3 and PC2 convertases. ► Proinsulin maturation chaos results in defects in the following conversion process. ► A link of the proinsulin maturation disorder and hyperproinsulinemia is suggested.