Biologic and Clinical Importance of Proinsulin

IN 1953 Sanger and Thompson described the complete covalent structure of insulin, a hormone containing two separate peptide chains and three disulfide bonds.1,2 Although proposed models for the biosynthesis of such a complex molecule were debated for many years, it was not until 1967 that the mechanism for insulin biosynthesis was finally elucidated: using an in vitro system containing isolated pancreatic islets or human insulinoma tissue and Radio-labeled amino acids, Steiner and his colleagues showed that the formation of insulin was preceded by the biosynthesis of a single-chain insulin-containing peptide about 1 1/2 times the size of insulin itself.3,4 Isolation . . .