Proinsulin

Literature References: Single chain insulin precursor consisting of the insulin A and B chains and a connecting polypeptide (C-peptide), which contains 30-35 amino acids; the number and sequence of these amino acids are species dependent. Its presence was discovered in a human islet cell adenoma: D. F. Steiner, P. E. Oyer, Proc. Natl. Acad. Sci. USA 57, 473 (1967). Conversion of proinsulin to insulin has a half-time of about 1 hour in rat islets in vitro; it is postulated that proteolytic enzymes cleave proinsulin at the sites where two amino acids connect the C-peptide to the insulin chain.This cleavage results in the production of insulin and the C-peptide, both of which are retained in the secretory granules of the beta cells and discharged in equimolar amounts during exocytosis of the granules. See W. Kemmler, D. F. Steiner, Biochem. Biophys. Res. Commun. 41, 1223 (1970). In vitro conversion of proinsulin to insulin with trypsin and carboxypeptidase B: W. Kemmler et al., J. Biol. Chem. 246, 6786(1971), 248, 4544 (1973). Isoln of bovine proinsulin: D. F. Steiner et al., Diabetes 17, 725 (1968). Structural studies on mammalian proinsulin: R. E. Chance et al., Science 161, 165 (1968) (porcine); C. Nolan et al., J. Biol. Chem. 246, 2780 (1971) (bovine); P. E. Oyer et al., ibid. 1365 (human, monkey); J. D. Petersen et al., ibid. 247, 4866 (1972) (monkey, sheep, dog); H. S. Tager, D. F. Steiner, ibid. 7936 (rat, horse); D. E. Massey, D. G. Smyth, ibid. 250, 628 (1975) (guinea pig). Proposed three-dimensional structure: C. R. Snell, D. G. Smyth, ibid. 6291. Syntheses of C-peptides and human proinsulin: N. Yanaihara et al., Diabetes 27(Suppl. 1), 149 (1978). Synthesis of rat proinsulin in bacteria: L. Villa-Komaroff et al., in Polypeptide Hormones, R. F. Beers, E. G. Bassett, Eds. (Raven Press, New York, 1980) pp 49-65. Reviews: D. F. Steiner et al. in Diabetes, 8th Proc. Congr. Int. Diabetes Fed., W. J. Malaisse, J. Pirart, Eds. (Excerpta Med., Amsterdam, 1974) pp 119-133; A. H. Rubenstein et al., in Recent Prog. Horm. Res. 33, R. O. Greep, Ed. (Academic Press, New York, 1977) pp 435-475; A. E. Kitabshi, Metabolism 26, 547-587 (1977). Book: Proinsulin, Insulin, C-Peptides, S. Baba et al., Eds. (Excerpta Medica, Amsterdam, 1979) 468 pp.