Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

A structurally abnormal insulin causing human diabetes

Abstract

Insulin isolated from the pancreas of a diabetic patient with fasting hyperinsulinaemia showed decreased activity in binding to cell membrane insulin receptors and in stimulating cellular 2-deoxyglucose transport and glucose oxidation. Chemical studies suggest that the isolated hormone is a mixture of normal insulin and an abnormal variant which contains a leucine for phenylalanine substitution at position 24 or 25 of the insulin B-chain.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Kahn, C. R. Metabolism 27, Suppl. 2, 1893–1902 (1978).

    Article  CAS  PubMed  Google Scholar 

  2. Kahn, C. R. et al. New Engl. J. Med. 244, 739–745 (1976).

    Article  Google Scholar 

  3. Kobayashi, M. et al. Proc. natn. Acad. Sci. U.S.A. 75, 3469–3473 (1978).

    Article  ADS  CAS  Google Scholar 

  4. Berson, S. A. & Yalow, R. S. in Diabetes Mellitus: Theory and Practice (eds Ellenberg, M. & Rifkin, H.) 388–423 (McGraw-Hill, New York, 1970).

    Google Scholar 

  5. Flier, J. S., Kahn, C. R., Roth, J. & Bar, R. S. Science 190, 63–65 (1975).

    Article  ADS  CAS  PubMed  Google Scholar 

  6. Muggeo, M. et al. New Engl. J. Med. 300, 477–489 (1979).

    Article  CAS  PubMed  Google Scholar 

  7. Bar, R. S. et al. Adv. int. Med. 24, 23–52 (1979).

    CAS  Google Scholar 

  8. Gabbay, K. H., DeLuca, K., Fisher, J. N. Jr, Mako, M. E. & Rubenstein, A. H. New Engl. J. Med. 294, 911–915 (1976).

    Article  CAS  PubMed  Google Scholar 

  9. Davoren, P. R. Biochim. biophys. Acta 63, 150–153 (1962).

    Article  CAS  PubMed  Google Scholar 

  10. Lowry, O. H., Rosenbrough, N. J., Farr, A. L. & Randall, R. J. J. biol. Chem. 193, 265–276 (1951).

    CAS  PubMed  Google Scholar 

  11. Humbel, R. E., Bosshard, H. R. & Zahn, H. in Handbook of Physiology Section 7 Vol. 1 (eds Steiner, D. F. & Freinkel, N.) 111–132 (Williams and Wilkins, Baltimore, 1972).

    Google Scholar 

  12. Starr, J. I. & Rubenstein, A. H. in Methods of Hormone Radioimmunoassay (eds Jaffe, B. M. & Behrman, H. R.) 289–305 (Academic, New York, 1974).

    Google Scholar 

  13. Davis, B. J. Ann. N.Y. Acad. Sci. 121, 404–422 (1964).

    Article  ADS  CAS  PubMed  Google Scholar 

  14. Reisfeld, R. A., Lewis, U. J. & Williams, D. E. Nature 195, 281–283 (1962).

    Article  ADS  CAS  PubMed  Google Scholar 

  15. Olefsky, J. M. J. clin. Invest. 58, 1450–1460 (1976).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gavin, J. R., Gorden, P., Roth, J., Archer, J. & Buell, D. J. biol. Chem. 246, 2202–2207 (1973).

    Google Scholar 

  17. Rodbell, M. J. biol. Chem. 239, 375–380 (1964).

    CAS  PubMed  Google Scholar 

  18. Glieman, J., Osterland, K., Vinten, J. & Gammeltoft, S. Biochim. biophys. Acta 286, 1–9 (1972).

    Article  Google Scholar 

  19. Woods, K. R. & Wang, K.-T. Biochim. biophys. Acta 133, 369–370 (1967).

    Article  CAS  PubMed  Google Scholar 

  20. Clark, J. L. & Steiner, D. F. Proc. natn. Acad. Sci. U.S.A. 62, 278–285 (1969).

    Article  ADS  CAS  Google Scholar 

  21. Smith, L. F. Am. J. Med. 40, 662–666 (1966).

    Article  CAS  PubMed  Google Scholar 

  22. Peterson, J. D., Steiner, D. F., Edmin, S. O. & Falkmer, S. J. biol. Chem. 250, 5183–5191 (1975).

    CAS  PubMed  Google Scholar 

  23. Weitzel, G., Bauer, F. & Eisele, K. Hoppe–Seyler's Z. physiol. Chem. 357, 187–200 (1976).

    Article  CAS  Google Scholar 

  24. Weitzel, G., Eisele, K., Schulz, V. & Stock, W. Hoppe–Seyler's Z. physiol. Chem. 354, 321–330 (1973).

    Article  CAS  Google Scholar 

  25. De Meyts, P., Van Obberghen, E., Roth, J., Wollmer, A. & Brandenburg, D. Nature 273, 504–509 (1978).

    Article  ADS  CAS  PubMed  Google Scholar 

  26. Blundell, T., Dodson, G., Hodgkin, D. & Mercola, D. Adv. Protein Chem. 26, 279–402 (1972).

    Article  CAS  Google Scholar 

  27. Edmin, S. O., Gammeltoft, S. & Gliemann, J. J. biol. Chem. 252, 602–608 (1977).

    Google Scholar 

  28. Muggeo, M., Ginsberg, B. H., Roth, J., De Meyts, P. & Falkmer, S. Diabetes 26, Suppl. 1, 353 (1977).

    Google Scholar 

  29. Wood, S. P., Blundell, T. L., Wollmer, A., Lazarus, N. R. & Neville, R. W. Eur. J. Biochem. 55, 531–542 (1975).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tager, H., Given, B., Baldwin, D. et al. A structurally abnormal insulin causing human diabetes. Nature 281, 122–125 (1979). https://doi.org/10.1038/281122a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/281122a0

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing