Title: Insulin
CAS Registry Number: 9004-10-8; 11061-68-0 (Human)
Literature 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).
Properties: Crystals, hexagonal system, usually obtained as flat rhombohedra and contg 0.4% Zn. Readily sol in dil acids and alkalies. Isoelectric point 5.30 to 5.35.
Derivative Type: Bovine insulin
CAS Registry Number: 11070-73-8
Trademarks: Hypurin (CP Pharm.)
Derivative Type: Porcine insulin
CAS Registry Number: 12584-58-6
Trademarks: Iletin II (Lilly); Velosulin (Novo)
Literature References: Differs from human insulin by a single amino acid substitution.
Derivative Type: Recombinant human insulin
Additional Names: Biosynthetic human insulin; insulin (prb)
Trademarks: Huminsulin (Lilly); Humulin (Lilly); Humulina (Lilly)
Literature References: Human insulin prepd by recombinant DNA technology. Clinical evaluation of inhaled intrapulmonary delivery in type 1 diabetes: J. S. Skyler et al., Lancet 357, 331 (2001); in type 2 diabetes: W. T. Cefalu et al., Ann. Intern. Med. 134, 203 (2001).
Derivative Type: Semi-synthetic human insulin
Additional Names: Insulin (emp)
Trademarks: Biohulin (Biobras); Novolin (Novo); Orgasuline (Organon)
Properties: Human insulin prepd by enzymatic modification of porcine insulin.
Derivative Type: Zinc insulin
CAS Registry Number: 8049-62-5
Literature References: Crystalline prepn of insulin containing 0.45-0.9% zinc. Formulated as suspensions in physiological saline; size of the particles determines the duration of action. Formulations are designated as prompt (or semilente), lente and extended (or ultralente).
Derivative Type: Protamine zinc insulin
CAS Registry Number: 9004-17-5
Additional Names: PZI insulin
Literature References: Suspensions of insulin modified by the addition of zinc chloride and protamine sulfate.
Properties: White or almost white suspension, pH 7.1-7.4. Onset of action occurs from 4-6 hrs after s.c. injection; duration of action is 36 hrs.
Derivative Type: Isophane insulin
Additional Names: NPH insulin; neutral protein Hagedorn insulin
Literature References: Crystallized prepn of protamine, zinc and insulin. Prepn: H. C. Hagedorn et al., J. Am. Med. Assoc. 106, 177 (1936). Review: P. Felig, ibid. 251, 393-396 (1984).
Properties: White suspensions of rod-shaped crystals ~30 nm in length, pH 7.1-7.4. Onset of action is 3-4 hrs following s.c. injection; duration of action is 18-28 hrs.
Derivative Type: Insulin 131I
Additional Names: Radio-iodinated insulin
Literature References: Prepn: Burrows et al., J. Clin. Invest. 36, 393 (1957); Grodsky et al., Arch. Biochem. Biophys. 81, 264 (1959).
Use: Insulin 131I used in the study of insulin binding factors from insulin resistant sera.
Therap-Cat: Antidiabetic.
Keywords: Antidiabetic; Hormones/Analogs. |