Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Abnormal lymphocyte function precedes hyperglycaemia in mice treated with multiple low doses of streptozotocin

  • 56 Accesses

  • 16 Citations


To investigate early immunological disturbances at the onset of diabetes, lymphocyte function and islet cell surface antibodies were studied in streptozotocin-treated C57BL/10 and B10.BR mice. In C57BL/10 mice, streptozotocin given in multiple low doses depressed lymphoblastic transformation to phytohaemagglutinin and pokeweed mitogen, but not to concanavalin A on day 6 after the first administration. On day 20, the transformation remained suppressed with phytohaemagglutinin, but recovered to the control level with pokeweed mitogen. In the early phase after treatment, the islet cell surface antibodies were elevated and then declined. Single high dose administration depressed responses to phytohaemagglutinin with no detectable islet cell surface antibodies. In B10.BR mice transformations to pokeweed mitogen and concanavalin A were suppressed in the early phase. The strain of mice may be a factor to be considered. Thus, it was suggested that the deterioration of immunological function with the formation of islet cell surface antibodies preceded the onset of hyperglycaemia in mice treated with multiple low doses of streptozotocin.


  1. 1.

    Lendrum R, Walker G, Gamble DR (1975) Islet-cell antibodies in juvenile diabetes mellitus of recent onset. Lancet 1: 880–883

  2. 2.

    Srikanta S, Ganda OP, Eisenbarth GS, Soeldner JS (1983) Islet-cell antibodies and beta-cell function in monozygotic triplets and twins initially discordant for Type 1 diabetes mellitus. N Engl J Med 308: 322–325

  3. 3.

    Lermark A, Freedman ZR, Hofmann C, Rubenstein AH, Steiner DF, Jackson RL, Winter RJ, Traisman HS (1978) Islet-cell-surface antibodies in juvenile diabetes mellitus. N Engl J Med 299: 375–380

  4. 4.

    Like AA, Rossini AA (1976) Streptozotocin-induced pancreatic insulitis: new model of diabetes mellitus. Science 193: 415–417

  5. 5.

    MacCuish AC, Urbaniak SJ, Campbell CJ, Duncan LJP, Irvine WJ (1974) Phytohemagglutinin transformation and circulating lymphocyte subpopulations in insulin-dependent diabetic patients. Diabetes 23: 708–712

  6. 6.

    Rakieten N, Rakieten ML, Nadkarni M (1963) Studies on the diabetogenic action of streptozotocin. Cancer Chemother Rep 29: 91–98

  7. 7.

    Rossini AA, Williams RM, Appel MC, Like AA (1978) Complete protection from low-dose streptozotocin-induced diabetes in mice. Nature 276:182–184

  8. 8.

    Leiter EH, Beamer WG, Shultz LD (1983) The effect of immunosuppression on streptozotocin-induced diabetes in C57BL/KsJ mice. Diabetes 32: 148–155

  9. 9.

    Nedergaard M, Egeberg J, Kromann H (1983) Irradiation protects against pancreatic islet degeneration and hyperglycaemia following streptozotocin treatment of mice. Diabetologia 24: 382–386

  10. 10.

    Kiesel U, Freytag G, Biener J, Kolb H (1980) Transfer of experimental autoimmune insulitis by spleen cells in mice. Diabetologia 19: 516–520

  11. 11.

    Dobersen MJ, Scharff JE, Ginsberg-Fellner F, Notkins AL (1980) Cytotoxic autoantibodies to beta cells in the serum of patients with insulin-dependent diabetes mellitus. N Engl J Med 303: 1493–1498

  12. 12.

    Eisenbarth GS, Morris MA, Scearce RM (1981) Cytotoxic antibodies to cloned rat islet cells in serum of patients with diabetes mellitus. J Clin Invest 67: 403–408

  13. 13.

    Kromann H, Lernmark A, Vestergaard BF, Egeberg J, Nerup J (1979) The influence of the major histocompatibility complex (H-2) on experimental diabetes in mice. Diabetologia 16: 107–114

  14. 14.

    Kiesel U, Kolb H (1982) Low-dose streptozotocin-induced autoimmune diabetes is under the genetic control of the major histocompatibility complex in mice. Diabetologia 23: 69–71

  15. 15.

    Kromann H, Christy M, Egeberg J, Lernmark A, Nerup J (1982) Absence of H-2 genetic influence on streptozotocin-induced diabetes in mice. Diabetologia 23:114–118

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Itoh, M., Funauchi, M., Sato, K. et al. Abnormal lymphocyte function precedes hyperglycaemia in mice treated with multiple low doses of streptozotocin. Diabetologia 27, 109–112 (1984). https://doi.org/10.1007/BF00275662

Download citation

Key words

  • Lymphocyte function
  • experimental diabetes
  • islet cell surface antibody
  • streptozotocin
  • mice
  • insulitis