Enzymatic destruction of immunoreactivity in proinsulin and insulin and activation of their scrambled forms

The enzyme glutathione-insulin transhydrogenase, that catalyzes sulfhydryldisulfide interchange, inactivates both insulin and proinsulin; the inactivation of insulin takes place at a greater rate than that of proinsulin. Under the experimental conditions used, the enzyme reactivates scrambled proinsulin but does not reactivate scrambled insulin. However, in the presence of connecting peptide of proinsulin reactivation of scrambled insulin is observed, indicating that for the generation of immunoreactive insulin covalent binding of C-peptide is not necessary and residues 31, 32, 59, and 60 of proinsulin may be omitted.