Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

New approaches to therapy and diagnosis of diabetes

  • 72 Accesses

  • 2 Citations


Not only has recombinant DNA added another source of insulin for treatment, but also, and perhaps more important, it has allowed the development of new techniques for studying the structure and function of the B cell at the gene level. We can only hope that this information will bring us closer to the understanding of the disease, so the diabetic patient may benefit from other measures of treatment than the classical replacement therapy introduced by Banting and Best 60 years ago [47].


  1. 1.

    Riggs AD, Itakura K, Crea R, Hirose T, Kraszewski A, Goeddel D, Kleid D, Yansura DG, Bolivar T, Heyneker HL (1980) Synthesis, cloning and expression of hormone genes in Escherichia coli. Recent Prog Horm Res 36: 261–276

  2. 2.

    Miller WL (1979) Use of recombinant DNA for the production of polypeptides. In: Petriccinai C, Hopps HE, Chapple PS (eds) Cell substrates; their use in the production of biologicals. Plenum Press, New York, pp 153–174

  3. 3.

    Miller WL, Baxter JD (1980) Recombinant DNA — A new source of insulin. Diabetologia 18: 431–436

  4. 4.

    Goeddel DV, Kleid DG, Bolivar F, Heyneker HL, Yansura DG, Crea R, Hirose T, Kraszewski A, Itakura K, Riggs AD (1979) Expression in Escherichia coli of chemically synthesized genes for human insulin. Proc Natl Acad Sci USA 76: 106–110

  5. 5.

    Ryle AP, Sanger F, Smith LF, Kitai Ruth (1955) The disulphide bonds of insulin. Biochem J 60: 541–556

  6. 6.

    Brown H, Sanger F, Kitai Ruth (1955) The structure of pig and sheep insulin. Biochem J 60: 556–565

  7. 7.

    Smith LF (1972) Amino acid sequences of insulins. Diabetes 21: 457–460

  8. 8.

    Nicol DSHW, Smith LF (1960) Amino-acid sequence of human insulin. Nature 187: 483–485

  9. 9.

    Bloom SR, West AM, Polak JM, Barnes AJ, Adrian TE (1970) Hormonal contaminants of insulin. In: Bloom SR (ed) Gut hormones. Churchill Livingstone, Edinburgh London New York, pp 318–322

  10. 10.

    Smith LF (1964) Isolation of insulin from pancreatic extracts using carboxymethyl and diethylaminoethyl celluloses. Biochim Biophys Acta 82: 231–236

  11. 11.

    Brunfeldt K, Deckert T, Thomsen J (1969) Human crystalline insulin from non-diabetic and diabetic patients. Acta Endocrinol (Copenhagen) 60: 543–549

  12. 12.

    Katsoyannis PG, Tometsko A, Fukuda K (1963) Insulin peptides. IX. The synthesis of the A-chain of insulin and its combination with natural B-chain to generate insulin activity. J Am Chem Soc 85: 2863–2865

  13. 13.

    Meinhofer J, Schnabel E, Bremer H, Brinhoff O, Zabel R, Sroka W, Klostermeyer H, Brandenburg D, Okuda T, Zahn H (1963) Synthese der Insulinketten und ihre Kombination zu insulinaktiven Präparaten. Z Naturforsch 18b: 1120–1121

  14. 14.

    Sieber K, Kamber B, Hartmann A, Jöhl A, Riniker B, Rittel W (1974) Totalsynthese von Humaninsulin gezielter Bildung der Disulfidbindungen. Helv Chim Acta 57: 2617–2621

  15. 15.

    Märki F, Albrecht W (1977) Biological activity of synthetic human insulin. Diabetologia 13: 293–295

  16. 16.

    Teuscher A (1979) Die biologische Wirkung von vollsynthetischem humanem Insulin bei Patienten mit Diabetes mellitus. Schweiz Med Wochenschr 109: 743–747

  17. 17.

    Diem P, Teuscher A (1979) Immunologische Untersuchungen mit vollsynthetischem humanem Insulin bei Patienten mit Diabetes mellitus. Schweiz Med Wochenschr 109: 1814–1816

  18. 18.

    Schmitt EW, Gattner H-G (1978) Verbesserte Darstellung von Des-alanylB30-insulin. Hoppe-Seyler's Z Physiol Chem 359: 799–802

  19. 19.

    Morihara K, Oka T, Tsuzuki H (1979) Semi-synthesis of human insulin by trypsin-catalysed replacement of Ala-B30 by Thr in porcine insulin. Nature 280: 412–413

  20. 20.

    Crea R, Kraszewski A, Hirose T, Itakura K (1978) Chemical synthesis of genes for human insulin. Proc Natl Acad Sci USA 75: 5765–5769

  21. 21.

    Riggs AD, Itakura K (1979) Synthetic DNA and medicine. Am J Hum Genet 31: 531–538

  22. 22.

    Chance RE, Kroeff PE, Hoffmann JA (1981) Chemical physical and biological properties of recombinant human insulin. In: Gueriguian JL, Miller HI, Schaffenburg CA, Gregoire AT, Sobel S (eds) Insulins, growth hormone and recombinant DNA technology. Raven Press, New York, pp 71–86

  23. 23.

    Keen H, Pickup JC, Bilous RW, Glynne A, Viberty GC, Jarrett RJ (1980) Human insulin produced by recombinant DNA technology: Safety and hypoglycaemic potency in healthy men. Lancet 2: 398–401

  24. 24.

    Klostermeyer H, Humbel RE (1966) Chemistry and biochemistry of insulin. Angew Chem Int Ed Engl 5: 807–822

  25. 25.

    Jeffrey PD (1974) Polymerization behaviour of bovine zinc-insulin at neutral pH. Molecular weight of the submit and the effect of glucose. Biochemistry 13: 4441–4447

  26. 26.

    Cunningham LW, Fischer RL, Vestling CS (1955) A study of the binding of zinc and cobalt by insulin. J Am Chem Soc 77: 5703–5707

  27. 27.

    Hansen B, Nielsen JH, Welinder B (in press) Immunogenicity of insulin in relation to its physico-chemical properties. In: Erb P, Keck K (eds) Basic and clinical aspects of immunity to insulin, de Gruyter, Berlin, pp 335–352

  28. 28.

    Berson SA, Yalow RS (1956) Insulin-131I metabolism in human subjects: demonstration of insulin binding globulin in the circulation of insulin treated subjects. J Clin Invest 35: 170–190

  29. 29.

    Deckert T (1964) Insulin antibodies. MD Thesis, Munksgaard, Copenhagen

  30. 30.

    Chance RE, Root MA, Galloway JA (1976) The immunogenicity of insulin preparations. Acta Endocrinol (Copenhagen) 205 (Suppl): 185–196

  31. 31.

    Grabar D, Fankhauser S (1978) Die Antigenicität einiger neuer, chromatographisch gereinigter Depot-Insulin-Präparate. Schweiz Med Wochenschr 108: 1807–1809

  32. 32.

    Neubauer HP, Schöne HH (1978) The immunogenicity of different insulin in several animal sources. Diabetes 27: 8–15

  33. 33.

    Deckert T, Andersen OV, Grundahl E, Kerp L (1972) Isoimmunization of man by recrystallized human insulin. Diabetologia 8: 358–361

  34. 34.

    Hansen B (1981) Immunogenicity of insulin as a function of species and other factors. In: Gueriguian JL, Miller HI, Schaffenburg CA, Gregoire AT, Sobel S (eds) Insulins, growth hormone, and recombinant DNA technology. Raven Press, New York, pp 55–70

  35. 35.

    Ullrich A, Shine J, Chirgwin J, Pictet R, Tischer E, Rutter WJ, Goodman HM (1977) Rat insulin genes: construction of plasmids containing the coding sequences. Science 496: 1313–1319

  36. 36.

    Bell GI, Swain WF, Pictet R, Cordell B, Goodman HM, Rutter WJ (1979) Nucleotide sequence of a cDNA clone containing human pre-proinsulin. Nature 282: 525–427

  37. 37.

    Cordell B, Bell G, Tischer E, Denoto FM, Ullrich A, Pictet R, Rutter WJ, Goodman HM (1979) Isolation and characterization of a cloned rat insulin gene. Cell 18: 533–543

  38. 38.

    Lomedico P, Rosenthal N, Efstradiadis A, Gilbert W, Kolodner R, Tizard R (1979) The structure and evolution of the two nonallelic rat pre-proinsulin genes. Cell 18: 545–558

  39. 39.

    Bell GI, Pictet R, Rutter WJ, Cordell B, Tischer E, Goodman HM (1980) Sequence of the human insulin gene. Nature 284: 26–32

  40. 40.

    Owerbach D, Bell GI, Rutter WJ, Shows TB (1980) The insulin gene is located on chromosome 11 in humans. Nature 286: 82–84

  41. 41.

    Owerbach D, Bell GI, Rutter WJ, Brown JA, Shows TB (1981) The insulin gene is located on the short arm of chromosome 11. Diabetes 30: 267–270

  42. 42.

    Gabbay KH (1980) The insulinopathies. N Engl J Med 302: 165–167

  43. 43.

    Gabbay KH, Bergenstal RM, Wolff J, Mako ME, Rubenstein AH (1979) Familial hyperinsulinemia: partial characterization of circulating proinsulin-like material. Proc Natl Acad Sci USA 76: 2881–2885

  44. 44.

    Kanazawa Y, Hayashi M, Ikeuchi M, Hiramatsu K, Kosaka K (1978) Familial proinsulinemia: a possible cause of abnormal glucose tolerance. Eur J Clin Invest 8: 327 (Abstract)

  45. 45.

    Tager H, Given B, Baldwin D, Mako M, Markese J, Rubenstein AH, Olefsky J, Kobayashi M, Kolterman O, Poucher R (1979) A structurally abnormal insulin causing human diabetes. Nature 281: 122–125

  46. 46.

    Owerbach D, Nerup J (1981) Restriction fragment length polymorphism of the insulin gene in diabetic individuals. Diabetologia 21: 311 (Abstract)

  47. 47.

    Best CH (1960) Forty years of interest in insulin. Br Med Bull 16: 179–182

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Hansen, B., Lernmark, Å., Nielsen, J.H. et al. New approaches to therapy and diagnosis of diabetes. Diabetologia 22, 61–67 (1982).

Download citation

Key words

  • Insulin preparations
  • porcine insulin
  • bovine insulin
  • human insulin
  • recombinant DNA
  • insulin gene
  • polymorphism