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. 1984 Oct;117(1):92–97.

Prevention of diabetes mellitus in the BB/W rat with Cyclosporin-A.

A A Like, V Dirodi, S Thomas, D L Guberski, A A Rossini
PMCID: PMC1900571  PMID: 6385729

Abstract

Autoimmune diabetes mellitus occurs spontaneously in 40-60% of a colony of BioBreeding/Worcester rats. Pretreatment of susceptible animals for 10-day intervals prior to 70 days of age with Cyclosporin-A (CSA) significantly reduced the frequency and delayed the onset of diabetes. The relatively narrow time frame of successful treatment suggests that effector cells responsible for beta cell destruction in this model of Type I diabetes may be activated during this period of time prior to the onset of overt hyperglycemia. CSA administration did not protect against the occurrence of lymphocytic thyroiditis or autoantibodies directed against smooth muscle or thyroid colloid, suggesting that these BB immunologic phenomena may be controlled by a distinct series of immunologic events.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alinaji, Silvers W. K., Bellgrau D., Anderson A. O., Plotkin S., Barker C. F. Prevention of diabetes in rats by bone marrow transplantation. Ann Surg. 1981 Sep;194(3):328–338. doi: 10.1097/00000658-198109000-00011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Borel J. F., Feurer C., Gubler H. U., Stähelin H. Biological effects of cyclosporin A: a new antilymphocytic agent. Agents Actions. 1976 Jul;6(4):468–475. doi: 10.1007/BF01973261. [DOI] [PubMed] [Google Scholar]
  3. Borel J. F., Feurer C., Magnée C., Stähelin H. Effects of the new anti-lymphocytic peptide cyclosporin A in animals. Immunology. 1977 Jun;32(6):1017–1025. [PMC free article] [PubMed] [Google Scholar]
  4. Butler L., Guberski D. L., Like A. A. Genetic analysis of the BB/W diabetic rat. Can J Genet Cytol. 1983 Feb;25(1):7–15. doi: 10.1139/g83-002. [DOI] [PubMed] [Google Scholar]
  5. Calne R. Y., Rolles K., White D. J., Thiru S., Evans D. B., McMaster P., Dunn D. C., Craddock G. N., Henderson R. G., Aziz S. Cyclosporin A initially as the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases, and 2 livers. Lancet. 1979 Nov 17;2(8151):1033–1036. doi: 10.1016/s0140-6736(79)92440-1. [DOI] [PubMed] [Google Scholar]
  6. Colle E., Guttmann R. D., Seemayer T. Spontaneous diabetes mellitus syndrome in the rat. I. Association with the major histocompatibility complex. J Exp Med. 1981 Oct 1;154(4):1237–1242. doi: 10.1084/jem.154.4.1237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Elder M., Maclaren N., Riley W., McConnell T. Gastric parietal cell and other autoantibodies in the BB rat. Diabetes. 1982 Apr;31(4 Pt 1):313–318. doi: 10.2337/diab.31.4.313. [DOI] [PubMed] [Google Scholar]
  8. Hess A. D., Donnenberg A. D., Tutschka P. J., Santos G. W. Effect of cyclosporin A on human lymphocyte responses in vitro. V. Analysis of responding T lymphocyte subpopulations in primary MLR with monoclonal antibodies. J Immunol. 1983 Feb;130(2):717–721. [PubMed] [Google Scholar]
  9. Jackson R., Rassi N., Crump T., Haynes B., Eisenbarth G. S. The BB diabetic rat. Profound T-cell lymphocytopenia. Diabetes. 1981 Oct;30(10):887–889. doi: 10.2337/diab.30.10.887. [DOI] [PubMed] [Google Scholar]
  10. Koevary S., Rossini A., Stoller W., Chick W., Williams R. M. Passive transfer of diabetes in the BB/W rat. Science. 1983 May 13;220(4598):727–728. doi: 10.1126/science.6836309. [DOI] [PubMed] [Google Scholar]
  11. Laupacis A., Stiller C. R., Gardell C., Keown P., Dupre J., Wallace A. C., Thibert P. Cyclosporin prevents diabetes in BB Wistar rats. Lancet. 1983 Jan 1;1(8314-5):10–12. doi: 10.1016/s0140-6736(83)91558-1. [DOI] [PubMed] [Google Scholar]
  12. Leapman S. B., Filo R. S., Smith E. J., Smith P. G. In vitro effects of cyclosporin A on lymphocyte subpopulations. 1. Suppressor cell sparing by cyclosporin A. Transplantation. 1980 Dec;30(6):404–408. doi: 10.1097/00007890-198012000-00003. [DOI] [PubMed] [Google Scholar]
  13. Like A. A., Anthony M., Guberski D. L., Rossini A. A. Spontaneous diabetes mellitus in the BB/W rat. Effects of glucocorticoids, cyclosporin-A, and antiserum to rat lymphocytes. Diabetes. 1983 Apr;32(4):326–330. doi: 10.2337/diab.32.4.326. [DOI] [PubMed] [Google Scholar]
  14. Like A. A., Appel M. C., Rossini A. A. Autoantibodies in the BB/W rat. Diabetes. 1982 Sep;31(9):816–820. doi: 10.2337/diab.31.9.816. [DOI] [PubMed] [Google Scholar]
  15. Like A. A., Butler L., Williams R. M., Appel M. C., Weringer E. J., Rossini A. A. Spontaneous autoimmune diabetes mellitus in the BB rat. Diabetes. 1982;31(Suppl 1 Pt 2):7–13. doi: 10.2337/diab.31.1.s7. [DOI] [PubMed] [Google Scholar]
  16. Like A. A., Kislauskis E., Williams R. R., Rossini A. A. Neonatal thymectomy prevents spontaneous diabetes mellitus in the BB/W rat. Science. 1982 May 7;216(4546):644–646. doi: 10.1126/science.7041259. [DOI] [PubMed] [Google Scholar]
  17. Like A. A., Rossini A. A., Guberski D. L., Appel M. C., Williams R. M. Spontaneous diabetes mellitus: reversal and prevention in the BB/W rat with antiserum to rat lymphocytes. Science. 1979 Dec 21;206(4425):1421–1423. doi: 10.1126/science.388619. [DOI] [PubMed] [Google Scholar]
  18. Naji A., Silvers W. K., Bellgrau D., Barker C. F. Spontaneous diabetes in rats: destruction of islets is prevented by immunological tolerance. Science. 1981 Sep 18;213(4514):1390–1392. doi: 10.1126/science.6791286. [DOI] [PubMed] [Google Scholar]
  19. Naji A., Silvers W. K., Kimura H., Bellgrau D., Markmann J. F., Barker C. F. Analytical and functional studies on the T cells of untreated and immunologically tolerant diabetes-prone BB rats. J Immunol. 1983 May;130(5):2168–2172. [PubMed] [Google Scholar]
  20. Naji A., Silvers W. K., Plotkin S. A., Dafoe D., Barker C. F. Successful islet transplantation in spontaneous diabetes. Surgery. 1979 Aug;86(2):218–226. [PubMed] [Google Scholar]
  21. Nakhooda A. F., Like A. A., Chappel C. I., Murray F. T., Marliss E. B. The spontaneously diabetic Wistar rat. Metabolic and morphologic studies. Diabetes. 1977 Feb;26(2):100–112. doi: 10.2337/diab.26.2.100. [DOI] [PubMed] [Google Scholar]
  22. Nussenblatt R. B., Rodrigues M. M., Wacker W. B., Cevario S. J., Salinas-Carmona M. C., Gery I. Cyclosporin a. Inhibition of experimental autoimmune uveitis in Lewis rats. J Clin Invest. 1981 Apr;67(4):1228–1231. doi: 10.1172/JCI110138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Poussier P., Nakhooda A. F., Falk J. A., Lee C., Marliss E. B. Lymphopenia and abnormal lymphocyte subsets in the "BB" rat: relationship to the diabetic syndrome. Endocrinology. 1982 May;110(5):1825–1827. doi: 10.1210/endo-110-5-1825. [DOI] [PubMed] [Google Scholar]
  24. Powles R. L., Clink H. M., Spence D., Morgenstern G., Watson J. G., Selby P. J., Woods M., Barrett A., Jameson B., Sloane J. Cyclosporin A to prevent graft-versus-host disease in man after allogeneic bone-marrow transplantation. Lancet. 1980 Feb 16;1(8164):327–329. doi: 10.1016/s0140-6736(80)90881-8. [DOI] [PubMed] [Google Scholar]
  25. Rossini A. A., Mordes J. P., Pelletier A. M., Like A. A. Transfusions of whole blood prevent spontaneous diabetes mellitus in the BB/W rat. Science. 1983 Feb 25;219(4587):975–977. doi: 10.1126/science.6823559. [DOI] [PubMed] [Google Scholar]
  26. Rossini A. A., Williams R. M., Mordes J. P., Appel M. C., Like A. A. Spontaneous diabetes in the gnotobiotic BB/W rat. Diabetes. 1979 Nov;28(11):1031–1032. doi: 10.2337/diab.28.11.1031. [DOI] [PubMed] [Google Scholar]
  27. Sternthal E., Like A. A., Sarantis K., Braverman L. E. Lymphocytic thyroiditis and diabetes in the BB/W rat. A new model of autoimmune endocrinopathy. Diabetes. 1981 Dec;30(12):1058–1061. doi: 10.2337/diab.30.12.1058. [DOI] [PubMed] [Google Scholar]
  28. Stiller C. R., Laupacis A., Keown P. A., Gardell C., Dupre J., Thibert P., Wall W. Cyclosporine: action, pharmacokinetics, and effect in the BB rat model. Metabolism. 1983 Jul;32(7 Suppl 1):69–72. doi: 10.1016/s0026-0495(83)80014-6. [DOI] [PubMed] [Google Scholar]
  29. Wang B. S., Heacock E. H., Chang-Xue Z., Tilney N. L., Strom T. B., Mannick J. A. Evidence for the presence of suppressor T lymphocytes in animals treated with cyclosporin A. J Immunol. 1982 Mar;128(3):1382–1385. [PubMed] [Google Scholar]
  30. White D. J., Plumb A. M., Pawelec G., Brons G. Cyclosporin A: an immunosuppressive agent preferentially active against proliferating T cells. Transplantation. 1979 Jan;27(1):55–58. [PubMed] [Google Scholar]

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