Skip to main content
SpringerLink
Log in

Administration of a nitric oxide synthase inhibitor does not suppress low-dose streptozotocin-induced diabetes in mice

  • Published:
International journal of pancreatology Aims and scope Submit manuscript

Summary

Nitric oxide (NO) has been reported as being a key mediator of the autoimmune destruction of B-cells in type I diabetes, and studies have described a suppression of low-dose streptozotocin-induced (LDS) diabetes in mice after the use of NO synthase inhibitors. However, these studies disagree with regard to the outcome of hyperglycemia and insulitis after treatment with thesel-arginine analogs. The present study tries to clarify this topic by administeringN-nitro-l-arginine-methylester (NAME) (15 mg/d/mouse/15 d) after an LDS treatment in 108 male C57BL6/J mice.

Glycemia measured at the end of the NAME treatment did show a slight, but significant, reduction when compared to LDS control animals (p<0.001), but values returned to diabetic levels 2 wk after withdrawal of NAME. Morphological observations demonstrated that the degree of infiltration and islet B-cell damage was absolutely not inhibited by NAME. In conclusion, treatment withl-arginine analogs is not capable of protecting mice from LDS-induced diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Mandrup-Poulsen T, Helqvist S, Wogensen LD, Molvig J, Pociot F, Johannesen J, Nerup J. Cytokines and free radicals as effector molecules in the destruction of pancreatic beta cells.Curr Topics Microbiol Immunol 1990; 164: 169–193.

    CAS  Google Scholar 

  2. Krönke K-D, Kolb-Bachofen V, Berschick B, Burkart V, Kolb H. Activated macrophages kill pancreatic syngeneic is let cells via arginine-dependent nitric oxide generation.Biochem Biophys Res Commun 1991; 175: 752–758.

    Article  Google Scholar 

  3. Corbett JA, McDaniel ML. Does nitric oxide mediate autoimmune destruction of B cells? Possible therapeutic interventions in IDDM.Diabetes 1992; 41: 897–903.

    Article  PubMed  CAS  Google Scholar 

  4. Kolb H, Kolb-Bachofen V. Nitricoxide: a pathogenetic factor in autoimmunity.Immunol Today 1992; 13: 157–159.

    Article  PubMed  CAS  Google Scholar 

  5. Mandrup-Poulsen T, Corbett JA, McDaniel M, Nerup J. What are the types and cellular sources of free radicals in the pathogenesis of type 1 insulin-dependent diabetes mellitus?Diabetologia 1993; 36: 470–473.

    Article  PubMed  CAS  Google Scholar 

  6. Nomikos IN, Wang Y, Lafferty KJ. Involvement of 02 radicals in autoimmune diabetes.Immunol Cell Biol 1989; 67: 85–87.

    Article  PubMed  CAS  Google Scholar 

  7. Papaccio G, Pisanti FA, Frascatore S. Acetyl-homocysteine-thiolactone-induced increase of superoxide dismutase counteracts the effect of subdiabetogenic doses of streptozocin.Diabetes 1986; 35: 470–474.

    Article  PubMed  CAS  Google Scholar 

  8. Mendola J, Wright JR, Lacy PE. Oxygen free radical scavengers and immune destruction of murine islets in allograft rejection and multiple low dose streptozocin-induced insulitis.Diabetes 1989; 38: 379–385.

    Article  PubMed  CAS  Google Scholar 

  9. Papaccio G. Prevention of low dose streptozocin-induced diabetes by acetyl-homocysteine-thiolactone.Diabetes Res Clin Practice 1991; 13: 95–102.

    Article  CAS  Google Scholar 

  10. Southern C, Schulster D, Green IC. Inhibition of insulin secretion by interleukin 1β and tumour necrosis factor-alpha via anl-arginine-dependent nitric oxide generating mechanism.FEBS Lett 1990; 276: 42–44.

    Article  PubMed  CAS  Google Scholar 

  11. Corbett JA, Wang JL, Sweetland MA, Lancaster JR, McDaniel ML. Il-1β induces the formation of nitric oxide by β cells purified from rodent in islets of langerhans: evidence for the β cell as a source and site of action of nitric oxide.J Clin Invest 1992; 90: 2384–2391.

    Article  PubMed  CAS  Google Scholar 

  12. Eizirik DL, Cagliero E, Björklund A, Welsh N. Interleukin-1β induces the expression of an isoform of nitric oxide synthase in insulin-producing cells, which is similar to that observed in activated macrophages.FEBS Lett 1992; 308: 249–252.

    Article  PubMed  CAS  Google Scholar 

  13. Krönke K-D, Rodriguez M-L, Kolb H, Kolb-Bachofen V: Cytotoxicity of activated rat macrophages against syngeneic islet cells is arginine-dependent, correlates with citrulline and nitrite concentrations and is identical to lysis by the nitric oxide donor nitroprusside.Diabetologia 1993; 36: 17–24.

    Article  Google Scholar 

  14. Kolb H, Kiesel U, Krönke K-D, Kolb-Bachofen V. Suppression of low dose streptozocin induced diabetes in mice by administration of nitric oxide synthase inhibitor.Life Sci 1991; 49: 213–217.

    Article  Google Scholar 

  15. Lukic ML, Stosic-Grujicic S, Ostojic N, Chan WL, Liew FY. Inhibition of nitric oxide generation affects the induction of diabetes by streptozocin in mice.Biochem Biophys Res Commun 1991; 178: 913–920.

    Article  PubMed  CAS  Google Scholar 

  16. Maclaren N, Lafferty K. The 12th International Immunology and Diabetes Workshop. Orlando, Florida.Diabetes 1993; 42: 1099–1104.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Anatomy, School of Medicine, 2nd University of Naples, 5 via Luciano Armanni, 80138, Naples, Italy

    Gianpaolo Papaccio, Vincenzo Esposito & Michael V. G. Latronico

  2. Institute of Forensic Toxicology, School of Medicine, 2nd University of Naples, 5 via Luciano Armanni, 80138, Naples, Italy

    Francesco Aurelio Pisanti

Authors
  1. Gianpaolo Papaccio
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vincenzo Esposito
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael V. G. Latronico
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francesco Aurelio Pisanti
    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

Papaccio, G., Esposito, V., Latronico, M.V.G. et al. Administration of a nitric oxide synthase inhibitor does not suppress low-dose streptozotocin-induced diabetes in mice. Int J Pancreatol 17, 63–68 (1995). https://doi.org/10.1007/BF02788360

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02788360

Key Words

Search

Navigation