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Differential Susceptibility of BALB/c Sublines to Diabetes Induction by Multi-Dose Streptozotocin Treatment

  • E. H. Leiter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 122)

Abstract

Streptozotocin (SZ), an antibiotic isolated from Streptomyces acromogenes, has potent diabetogenic activity in mice. Chemically, Sz consists of 2-deoxy-D-glucose coupled at the second carbon to a N-nitrosomethylurea side chain; targeting of this toxin to the pancreatic beta (β) cells probably is a function of the glucose ring whereas the cell damage is likely mediated via the alkylating activity of the N-nitroso moeity (Wilson et al. 1983). When Sz is administered at doses between 150–300 mg per kg body weight in a single bolus (either i.p. or i.v.), males and females of most inbred strains of mice will develop an insulin-dependent diabetic state within 72 hours post-injection. The diabetes is primarily the consequence of direct Sz-mediated cytotoxicity to the β-cells, and the ensuing hyperglycemia is permanent. Although mice made diabetic by a single high dose of Sz are often used as a model for juvenile onset (insulin-dependent) diabetes, the model is compromised because Sz also exerts direct toxic effects on the liver, kidneys, and on cells of the immune sytem, a fact which complicates analysis of the insulin deficient state.

Keywords

Major Histocompatibility Complex Inbred Strain Single High Dose Diabetes Induction Direct Cytotoxic Action 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Andersson A (1979) Islet implantation normalizes hyperglycemia caused by streptocin-induced insulitis. Lancet 1:581–584PubMedCrossRefGoogle Scholar
  2. Bailey CJ, Matty AJ (1972) Glucose tolerance and plasma insulin in the rat in relation to the oestrus cycle and sex hormones. Horm Metab Res 4:266–270PubMedCrossRefGoogle Scholar
  3. Bailey DW (1982) How pure are inbred strains of mice? Immunol Today 3:210–214CrossRefGoogle Scholar
  4. Beattie G, Lannom R, Lipsick J, Kaplan NO, Oster AG (1980) Streptozotocin-induced diabetes in athymic and conventional BALB/c mice. Diabetes 29:146–150PubMedCrossRefGoogle Scholar
  5. Bonnevie-Nielsen V, Steffes M, Lermark A (1981) A major loss in islet mass and B-cell function precedes hyperglycemia in mice given multiple low doses of streptozotocin. Diabetes 30:424–429PubMedCrossRefGoogle Scholar
  6. Buetti E, Diggelmann H (1981) Cloned mouse mammary tumor virus DNA is biologically active in transfected mouse cells and its expression is stimulated by glucocorticoid hormones. Cell 23:335–345PubMedCrossRefGoogle Scholar
  7. Buschard K, Rygaard J (1978) Is the diabetogenic effect of streptozotocin in part thymus-dependent? Acta path Microbiol Scand Sec. C-86:23–27Google Scholar
  8. Flaherty L (1981) Genes of theTla region: The new Qa system of antigens. In: Morse HC III (ed) Origins of inbred mice, Academic Press, New York, p. 409Google Scholar
  9. Grossman C (1985) Interactions between the gonadal steroids and the immune system. Science 227:257–261PubMedCrossRefGoogle Scholar
  10. Hoffman HA (1983) Profile of a genetic contamination: BALB/c-nu mice. ILAR NEWS 27:10–11Google Scholar
  11. Kamataki T, Maeda K, Yamazoe Y, Nagai T, Kato R (1983) Sex difference of cytochrome P-450 in the rat: purification, characterization, and quantitation of constitutive forms of cytochrome P-450 from liver microsomes of male and female rats. Arch Biochem Biophys 225:758–770PubMedCrossRefGoogle Scholar
  12. Kiesel U, Greulich B, Moume CM, Kolb H (1981) Induction of experimental autoimmune diabetes by low-dose streptozotocin treatment in genetically resistant mice. Immunol Lett 3:227–230PubMedCrossRefGoogle Scholar
  13. Kiesel U, Falkenberg FW, Kolb H (1983) Genetic control of low-dose streptozotocin-induced autoimmune diabetes in mice. J Immunol 130:1719–1722PubMedGoogle Scholar
  14. Klein D, Tewarson S, Figueroa F, Klein J (1982) The minimal length of the differential segment in H-2 congenic lines.Olmmunogenet 16:319–328CrossRefGoogle Scholar
  15. Kromann H, Christy M, Egeberg J, Lermark A, Nerup J (1982) Absence of H-2 genetic influence on streptozotocjn-induced diabetes in mice. Diabetologia 23:114–118PubMedCrossRefGoogle Scholar
  16. Kromann H, Christy M, Lemmark A, Nedergaard M, Nerup J (1982) The low-dose streptozotocin model of type I (insulin dependent) diabetes mellitus: studies in vivo and in vitro of the modulating effect of sex hormones. Diabetologia 22:194–198PubMedCrossRefGoogle Scholar
  17. Le PH, Leiter EH, Leyendecker JR (1985) Genetic controlof susceptibility to streptozotocin diabetes in inbred mice: effect of testosterone and H-2 haplotype. Endocrinology 116: in pressGoogle Scholar
  18. Leiter EH (1982) Multiple low-dose streptozotocin-induced hyperglycemia and insulitis in C57BL mice: Influence of inbred background, sex, and thymus. Proc Natl Acad Sci, USA 79:630–634PubMedCrossRefGoogle Scholar
  19. Leiter EH, Beamer WG, Shultz LD (1983) The effect of immunosuppression on strepto-zotocin-induced diabetes in C57BL/KsJ mice. Diabetes 32:148–155PubMedCrossRefGoogle Scholar
  20. Leiter EH (to be published) Induction of autoreactivity against islets in C57BL/KsJ mice: use of a transplantation model. DiabetesGoogle Scholar
  21. Like AA, Rossini AA (1976) Streptozotocin induced pancreatic insulitis: new model of diabetes mellitus. Science 193:415–417PubMedCrossRefGoogle Scholar
  22. MacLaren NK, Neufeld M, McLaughlin JV, Taylor G (1980) Androgen sensitization of streptozotocin-induced diabetes in mice. Diabetes 29:710–716PubMedGoogle Scholar
  23. Nakamura M, Nagafuchi S, Yamaguchi K, Takaki R (1984) The role of thymic immunity and insulitis in the development of streptozotocin-induced diabetes in mice. Diabetes 33:894–900PubMedCrossRefGoogle Scholar
  24. Paik S, Fleischer N, Shin S (1980) Insulin-dependent diabetes mellitus induced by subdiabetogenic doses of streptozotocin: obligatory role of cell mediated autoimmune processes. Proc Natl Acad Sci, USA 77:6129–6133PubMedCrossRefGoogle Scholar
  25. Ponta H, Rahmsdorf U, Butkeraitis P, Hynes NE, Groner B (1984) A transcriptional regulation sequence in the long terminal repeat of mouse mammary tumor virus has hormone induction and enhancer qualities. In: Endocrinology: proceedings of the International Congress of Endocrinology, Excerpta Medica, Amsterdam, p. IIIGoogle Scholar
  26. Rossini AA, Appel MC, Williams RC, Like AA (1977) Genetic influence of the strepto-zotocin-induced insulitis and hyperglycemia. Diabetes 26:916–920PubMedCrossRefGoogle Scholar
  27. Rossini AA, Williams RM, Appel MC, Like AA (1978a) Complete protection from low dose streptozotocin-induced diabetes in mice. Nature 276:182–184PubMedCrossRefGoogle Scholar
  28. Rossini AA, Williams RM, Appel MC, Like AA (1978b) Sex differences in the multiple dose streptozotocin model of diabetes. Endocrinology 103:1518–1520PubMedCrossRefGoogle Scholar
  29. Rossini AA, Williams RM, Appel MC, Like AA (1980) Animal models of the type 1 diabetes. In: Irvine J (ed) Immunology of diabetes, Teviot Scientific Publications, Edinburgh, p. 275Google Scholar
  30. Rouer E, LeProvost E, Leroux J-P (1983) Study of benzphetamine-N-demethylase in streptozotocin-diabetic mice and rats: evidence for the induction of catalytically and immunologically specific forms of cytochrome P450. Biochimie 65: 679–683PubMedCrossRefGoogle Scholar
  31. Vialettes B, Baume D, Chapin C, De Maeyer-Guignard J, Vague P (1983) Assessment of viral and immune factors in EMC virus-induced diabetes: effect of cyclosporin A and interferon. J Clin Lab Immunol 10:35–40PubMedGoogle Scholar
  32. Wilson GL, Mossman BT, Craighead JE (1983) Use of pancreatic beta cells in culture to identify diabetogenic N-nitroso compounds. In Vitro 19:25–30Google Scholar
  33. Wolf J, Lilly F, Shin S (1984) The influence of genetic background on the susceptibility of inbred mice to streptozotocin-induced diabetes. Diabetes 33:567–571PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1985

Authors and Affiliations

  • E. H. Leiter

There are no affiliations available

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