Insulin is an essential hormone for maintaining metabolic homeostasis in the body. To make
fully bioactive insulin, pancreatic beta cells initiate synthesis of the insulin precursor,
preproinsulin, at the cytosolic side of the endoplasmic reticulum (ER), whereupon it
undergoes co-and post-translational translocation across the ER membrane. Preproinsulin
is cleaved by signal peptidase to form proinsulin that folds on the luminal side of the ER,
forming three evolutionarily conserved disulfide bonds. Properly folded proinsulin forms …