Description and references

Polypeptide hormone produced by pancreatic beta cells that regulates carbohydrate homeostasis. Converted by proteolysis from the single chain proinsulin, q.v., to the active dimer composed of 51 amino acid residues; mol wt ≈6000. Regulates carbohydrate and lipid metabolism, and influences protein synthesis. Insulin was the first protein for which the chemical structure and mol wt were determined. Also the first commercial health care product produced by recombinant DNA technology. Because of its solubility at physiological pH, insulin is rapidly absorbed after subcutaneous injection. Various complexes with protamine and/or zinc have been prepd to improve drug delivery. In addition to biological source (human, porcine or bovine), insulin formulations for therapeutic use are classified according to onset and duration of action. Isoln: F. G. Banting, C. H. Best, J. Lab. Clin. Med. 7, 251 (1921-22). Crystallization: Abel, Proc. Natl. Acad. Sci. USA 12, 132 (1926). Purification and properties: J. Lens, Biochim. Biophys. Acta 2, 76 (1948). Complete amino acid sequence of bovine insulin: F. Sanger, H. Tuppy, Biochem. J. 49, 463, 481 (1951); F. Sanger, E. O. P. Thompson, ibid. 53, 353, 366 (1953). Identification of 2 chain structure: A. P. Ryle et al., ibid. 60, 541 (1955). Review of structure determination: F. Sanger, Science 129, 1340 (1959). Structure of human insulin: D. Nichol, L. F. Smith, Nature 187, 483 (1960). Crystal structure: D. C. Hodgkin, Verh. Schweiz. Naturforsch. Ges. 150, 93 (1970). Synthesis of human insulin: P. G. Katsoyannis et al., J. Am. Chem. Soc. 88, 164, 166 (1966); by the enzymatic modification of porcine insulin: M. A. Ruttenberg, Science 177, 623 (1972). Review of synthetic insulins: P. G. Katsoyannis, Recent Prog. Horm. Res. 23, 505-563 (1967). Synthesis of human insulin gene: H. M. Hsiung et al., Nucleic Acids Res. 6, 1371 (1979); 7, 2199 (1979); 8, 5753 (1980); S. A. Narang et al., Nucleic Acids Symp. Ser. 7, 377 (1980). Review of the development and production of human insulin by recombinant DNA technology: I. S. Johnson, Science 219, 632-637 (1983). Molecular basis of insulin action: M. P. Czech, Annu. Rev. Biochem. 46, 359 (1977). History: M. Bliss, The Discovery of Insulin (Univ. Chicago Press, Chicago, 1982) 304 pp. Review of biosynthesis: D. F. Steiner et al., Recent Prog. Horm. Res. 25, 207-282 (1969). Review of the structure and function of the insulin receptor: J. Lee, P. F. Pilch, Am. J. Physiol. 266, C319-C334 (1994). Symposium on the physiological regulation of insulin secretion and the pathogenesis of diabetes: Diabetologia 37, Suppl. 2, S1-S187 (1994). Review of bioactivity, pharmacokinetics and therapeutic efficacy of human insulin: R. N. Brogden, R. C. Heel, Drugs 34, 350-371 (1987). Review of insulin formulations and therapy: J. A. Galloway, R. E. Chance, Horm. Metab. Res. 26, 591-598 (1994); of analogs and alternative delivery methods: J. E. Gerich, Am. J. Med. 113, 308-316 (2002); of clinical development of inhaled formulations: L. D. Mastrandrea, T. Quattrin, Adv. Drug Delivery Rev. 58, 1061-1075 (2006).

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