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.

  • Letter
  • Published:

Streptozotocin and alloxan induce DNA strand breaks and poly(ADP–ribose) synthetase in pancreatic islets

Nature volume 294, pages 284–286 (1981)Cite this article

Abstract

Streptozotocin, which produces diabetes mellitus in experimental animals1–3, has been reported to reduce the level of NAD in pancreatic islets4,5 and to inhibit islet synthesis of proinsulin6. The decrease in NAD is due to increased NAD degradation mediated by islet nuclear poly(ADP–ribose) synthetase7,8. Evidence suggests that poly(ADP–ribose) synthetase is activated when DNA is fragmented9–17. Here we describe that both Streptozotocin and alloxan, which also produces experimental diabetes mellitus1,2, cause DNA strand breaks which stimulate nuclear poly(ADP–ribose) synthetase, thereby depleting intracellular NAD and inhibiting proinsulin synthesis in isolated pancreatic islets of rats.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Similar content being viewed by others

References

  1. Rerup, C. C. Pharmac. Rev. 22, 485–518 (1970).

    CAS  Google Scholar 

  2. Dulin, W. E. & Soret, M. G. in The Diabetic Pancreas (eds Volk, B. W. & Wellmann, K. F.) 425–465 (Plenum, New York, 1977).

    Book  Google Scholar 

  3. Agarwal, M. K. FEES Lett. 120, 1–3 (1980).

    Article  CAS  Google Scholar 

  4. Ho, C.-K. & Hashim, S. A. Diabetes 21, 789–793 (1972).

    Article  CAS  Google Scholar 

  5. Hinz, M., Katsilambros, N., Maier, V., Schatz, H. & Pfeiffer, E. F. FEBS Lett. 30, 225–228 (1973).

    Article  CAS  Google Scholar 

  6. Maldonato, A., Trueheart, P. A., Renold, A. E. & Sharp, G. W. G. Diabetologia 12, 471–481 (1976).

    Article  CAS  Google Scholar 

  7. Yamamoto, H. & Okamoto, H. Biochem. biophys. Res. Commun. 95, 474–481 (1980).

    Article  CAS  Google Scholar 

  8. Okamoto, H. Molec. cell. Biochem. 37, 43–61 (1981).

    Article  CAS  Google Scholar 

  9. Miller, E. G. Biochim. biophys. Acta 395, 191–200 (1975).

    Article  CAS  Google Scholar 

  10. Berger, N. A., Weber, G. & Kaichi, A. S. Biochim. biophys. Acta 519, 87–104 (1978).

    Article  CAS  Google Scholar 

  11. Smulson, M. E., Schein, P., Mullins, D. W. Jr & Sudhakar, S. Cancer Res. 37, 3006–3012 (1977).

    CAS  Google Scholar 

  12. Jacobson, M. K., Levi, V., Juarez-Salinas, H., Barton, R. A. & Jacobson, E. L. Cancer Res. 40, 1797–1802 (1980).

    CAS  PubMed  Google Scholar 

  13. Berger, N. A., Sikorski, G. W., Petzold, S. J. & Kurohara, K. K. Biochemistry 19, 289–293 (1980).

    Article  CAS  Google Scholar 

  14. Skidmore, C. J. et al. Eur. J. Biochem. 101, 135–142 (1979).

    Article  CAS  Google Scholar 

  15. Durkacz, B. W., Omidiji, O., Gray, D. A. & Shall, S. Nature 283, 593–596 (1980).

    Article  ADS  CAS  Google Scholar 

  16. Ohgushi, H., Yoshihara, K. & Kamiya, T. J. biol. Chem. 255, 6205–6211 (1980).

    CAS  PubMed  Google Scholar 

  17. Benjamin, R. C. & Gill, D. M. J. biol. Chem. 255, 10502–10508 (1980).

    CAS  PubMed  Google Scholar 

  18. Whish, W. J. D., Davies, M. I. & Shall, S. Biochem. biophys. Res. Commun. 65, 722–730 (1975).

    Article  CAS  Google Scholar 

  19. Smulson, M., Stark, P., Gazzoli, M. & Roberts, J. J. Expl Cell Res. 90, 175–182 (1975).

    Article  CAS  Google Scholar 

  20. Halldorsson, H., Gray, D. A. & Shall, S. FEBS Lett. 85, 349–352 (1978).

    Article  CAS  Google Scholar 

  21. Noto, Y. & Okamoto, H. Acta diabetol. lat. 15, 273–282 (1978).

    Article  CAS  Google Scholar 

  22. Itoh, N. & Okamoto, H. Nature 283, 100–102 (1980).

    Article  ADS  CAS  Google Scholar 

  23. Lacy, P. E., McDaniel, M. L., Fink, C. J. & Roth, C. Diabetologia 11, 501–507 (1975).

    Article  CAS  Google Scholar 

  24. Claycomb, W. C. Biochem. J. 154, 387–393 (1976).

    Article  CAS  Google Scholar 

  25. Levi, V., Jacobson, E. L. & Jacobson, M. K. FEBS Lett. 88, 144–146 (1978).

    Article  CAS  Google Scholar 

  26. Lazarow, A. Proc. Soc. exp. Biol. Med. 61, 441–447 (1946).

    Article  CAS  Google Scholar 

  27. Heikkila, R. E., Winston, B., Cohen, G. & Barden, H. Biochem. Pharmac. 25, 1085–1092 (1976).

    Article  CAS  Google Scholar 

  28. Grankvist, K., Marklund, S., Sehlin, J. & Täljedal, I.-B. Biochem. J. 182, 17–25 (1979).

    Article  CAS  Google Scholar 

  29. Fischer, L. J. & Hamburger, S. A. Diabetes 29, 213–216 (1980).

    Article  CAS  Google Scholar 

  30. Parkhurst, J. R., Peterson, A. R. & Heidelberger, C. Proc. natn. Acad. Sci. U.S.A. 70, 3200–3204 (1973).

    Article  ADS  CAS  Google Scholar 

  31. Berger, N. A., Weber, G., Kaichi, A. S. & Petzold, S. J. Biochim. biophys. Acta 519, 105–117 (1978).

    Article  CAS  Google Scholar 

  32. Okamoto, H., Noto, Y., Miyamoto, S., Mabuchi, H. & Takeda, R. FEBS Lett. 54, 103–105 (1975).

    Article  CAS  Google Scholar 

  33. Kissane, J. M. & Robins, E. J. biol. Chem. 233, 184–188 (1958).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Toyama Medical and Pharmaceutical University, School of Medicine, Toyama, 930-01, Japan

    Hiroshi Yamamoto, Yasuko Uchigata & Hiroshi Okamoto

Authors
  1. Hiroshi Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasuko Uchigata
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hiroshi Okamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yamamoto, H., Uchigata, Y. & Okamoto, H. Streptozotocin and alloxan induce DNA strand breaks and poly(ADP–ribose) synthetase in pancreatic islets. Nature 294, 284–286 (1981). https://doi.org/10.1038/294284a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/294284a0

This article is cited by

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

Advanced 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