INS and type 2 diabetes mellitus: Neither expression of the proinsulin-G(C28)R variant nor the mutants classically associated with adult-onset diabetes [F(B25)L or V(A3)L] activated the ER stress response in pancreatic beta cells, whereas proinsulin-F(B24)S generated an ER stress response that was intermediate between that of wild-type proinsulin and that observed for MIDY mutants (Fig. 8A).