The insulin molecule released into the circulation by the β cells of Langerhans' islets consists of two separate, straight polypeptide chains linked by disulfide bridges between and within the chains (Figure).1,2 These two chains are not separately manufactured; instead, the parent molecule synthesized on the ribosome consists of a larger precursor, proinsulin, a single coiled chain in which the amide terminus of the A-chain is linked to the carboxyl terminus of the B-chain by a connecting or C-peptide (Figure).1,2 Actually, an even larger precursor, pre-proinsulin, containing an additional peptide chain on the amino terminus of the A-chain is initially synthesized. This additional piece acts in a manner analogous to the leader in a film reel and is rapidly excised during synthesis.1,2 Further processing of proinsulin cleaves the C-peptide consisting of 31 amino acids from the insulin molecule at the sites indicated in the figure. As might be