INS and diabetes mellitus: On the other hand, we also recognize that MIDY mutant mice bearing the heterozygous Ins2-Munich allele—encoding proinsulin–C(A6)S—develop severe insulin-deficient diabetes [20], indicating that an unpaired proinsulin–Cys(A11) creates an impediment to proinsulin trafficking through disulfide mispairings [21] that can result in catastrophic proinsulin misfolding [19].