Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 May;87(10):3690–3694. doi: 10.1073/pnas.87.10.3690

Repopulation of the atrophied thymus in diabetic rats by insulin-like growth factor I.

K Binz 1, P Joller 1, P Froesch 1, H Binz 1, J Zapf 1, E R Froesch 1
PMCID: PMC53968  PMID: 2187189

Abstract

Atrophy of the thymus is one of the consequences of severe insulin deficiency. We describe here that the weight and the architecture of the thymus of diabetic rats is restored towards normal not only by insulin but also by insulin-like growth factor I (IGF-I) treatment. In contrast to insulin, this effect of IGF-I occurs despite persisting hyperglycemia and adrenal hyperplasia. We also investigated the in vivo effect of IGF-I on replication and differentiation of thymocytes from streptozotocin-induced diabetic rats. Thymocytes from diabetic rats incorporated less [3H]thymidine than did thymocytes from healthy rats. Insulin, as well as IGF-I treatment of diabetic rats increased [3H]thymidine incorporation by thymocytes. Flow cytometry of thymocytes labeled with monoclonal antibodies revealed a decreased expression of the Thy-1 antigen in diabetic rats compared with control rats. In addition, a major deficiency of thymocytes expressing simultaneously the W3/25 and the Ox8 antigens (corresponding to immature human CD4+/CD8+ thymocytes) was observed. These changes were restored towards normal by insulin as well as by IGF-I treatment. The antibody response to a T cell-dependent antigen (bovine serum albumin) was comparable in normal and diabetic rats. We conclude that IGF-I has important effects on the thymocyte number and the presence of CD4+/CD8+ immature cells in the thymus of diabetic rats despite persisting hyperglycemia. However, helper T-cell function for antibody production appears to be preserved even in the severely diabetic state.

Full text

PDF
3690

Images in this article

3692Image
on p.3692
3692Image
on p.3692
3692Image
on p.3692
3692Image
on p.3692

Selected References

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

  1. Adkins B., Mueller C., Okada C. Y., Reichert R. A., Weissman I. L., Spangrude G. J. Early events in T-cell maturation. Annu Rev Immunol. 1987;5:325–365. doi: 10.1146/annurev.iy.05.040187.001545. [DOI] [PubMed] [Google Scholar]
  2. Blomgren H., Andersson B. Characteristics of the immunocompetent cells in the mouse thymus: cell population changes during cortisone-induced atrophy and subsequent regeneration. Cell Immunol. 1970 Nov;1(5):545–560. doi: 10.1016/0008-8749(70)90041-9. [DOI] [PubMed] [Google Scholar]
  3. Drell D. W., Notkins A. L. Multiple immunological abnormalities in patients with type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1987 Mar;30(3):132–143. doi: 10.1007/BF00274217. [DOI] [PubMed] [Google Scholar]
  4. Fabris N., Piantanelli L. Differential effect of pancreatectomy on humoral and cell-mediated immune responses. Clin Exp Immunol. 1977 May;28(2):315–325. [PMC free article] [PubMed] [Google Scholar]
  5. Gaulton G. N., Schwartz J. L., Eardley D. D. Assessment of the diabetogenic drugs alloxan and streptozotocin as models for the study of immune defects in diabetic mice. Diabetologia. 1985 Oct;28(10):769–775. doi: 10.1007/BF00265026. [DOI] [PubMed] [Google Scholar]
  6. Guler H. P., Zapf J., Scheiwiller E., Froesch E. R. Recombinant human insulin-like growth factor I stimulates growth and has distinct effects on organ size in hypophysectomized rats. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4889–4893. doi: 10.1073/pnas.85.13.4889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hemmi S., Fenner M., Binz H., Winterhalter K., Wigzell H. Studies of monoclonal antibodies specific for major histocompatibility complex products of the rat. I. Production and characterization of monoclonal antibodies. Scand J Immunol. 1985 Jun;21(6):549–563. doi: 10.1111/j.1365-3083.1985.tb01845.x. [DOI] [PubMed] [Google Scholar]
  8. Ishibashi T., Kitahara Y., Harada Y., Harada S., Takamoto M., Ishibashi T. Immunologic features of mice with streptozotocin-induced diabetes: depression of their immune responses to sheep red blood cells. Diabetes. 1980 Jul;29(7):516–523. doi: 10.2337/diab.29.7.516. [DOI] [PubMed] [Google Scholar]
  9. Kelley K. W. Growth hormone, lymphocytes and macrophages. Biochem Pharmacol. 1989 Mar 1;38(5):705–713. doi: 10.1016/0006-2952(89)90222-0. [DOI] [PubMed] [Google Scholar]
  10. Kitahara Y., Ishibashi T., Harada Y., Takamoto M., Tanaka K. Reduced resistance to Pseudomonas septicaemia in diabetic mice. Clin Exp Immunol. 1981 Mar;43(3):590–598. [PMC free article] [PubMed] [Google Scholar]
  11. Maes M., Ketelslegers J. M., Underwood L. E. Low plasma somatomedin-C in streptozotocin-induced diabetes mellitus. Correlation with changes in somatogenic and lactogenic liver binding sites. Diabetes. 1983 Nov;32(11):1060–1069. doi: 10.2337/diab.32.11.1060. [DOI] [PubMed] [Google Scholar]
  12. Mahmoud A. A., Rodman H. M., Mandel M. A., Warren K. S. Induced and spontaneous diabetes mellitus and suppression of cell-mediated immunologic responses. Granuloma formation, delayed dermal reactivity and allograft rejection. J Clin Invest. 1976 Feb;57(2):362–367. doi: 10.1172/JCI108287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McDevitt H. O., Benacerraf B. Genetic control of specific immune responses. Adv Immunol. 1969;11:31–74. doi: 10.1016/s0065-2776(08)60477-0. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Nichols W. K., Spellman J. B., Vann L. L., Daynes R. A. Immune responses of diabetic animals. Direct immunosuppressant effects of streptozotocin in mice. Diabetologia. 1979 Jan;16(1):51–57. doi: 10.1007/BF00423151. [DOI] [PubMed] [Google Scholar]
  16. Paterson D. J., Green J. R., Jefferies W. A., Puklavec M., Williams A. F. The MRC OX-44 antigen marks a functionally relevant subset among rat thymocytes. J Exp Med. 1987 Jan 1;165(1):1–13. doi: 10.1084/jem.165.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Phillips L. S., Young H. S. Nutrition and somatomedin. II. Serum somatomedin activity and cartilage growth activity in streptozotocin-diabetic rats. Diabetes. 1976 Jun;25(6):516–527. doi: 10.2337/diab.25.6.516. [DOI] [PubMed] [Google Scholar]
  18. Rebuffat P., Belloni A. S., Malendowicz L. K., Mazzocchi G., Meneghelli V., Nussdorfer G. G. Effects of streptozotocin-induced experimental diabetes on the morphology and function of the zona fasciculata of rat adrenal cortex. Virchows Arch B Cell Pathol Incl Mol Pathol. 1988;56(1):13–19. doi: 10.1007/BF02889996. [DOI] [PubMed] [Google Scholar]
  19. Robinson I. C., Clark R. G., Carlsson L. M. Insulin, IGF-I and growth in diabetic rats. Nature. 1987 Apr 9;326(6113):549–549. doi: 10.1038/326549a0. [DOI] [PubMed] [Google Scholar]
  20. Saiki O., Negoro S., Tsuyuguchi I., Yamamura Y. Depressed immunological defence mechanisms in mice with experimentally induced diabetes. Infect Immun. 1980 Apr;28(1):127–131. doi: 10.1128/iai.28.1.127-131.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Scheiwiller E., Guler H. P., Merryweather J., Scandella C., Maerki W., Zapf J., Froesch E. R. Growth restoration of insulin-deficient diabetic rats by recombinant human insulin-like growth factor I. Nature. 1986 Sep 11;323(6084):169–171. doi: 10.1038/323169a0. [DOI] [PubMed] [Google Scholar]
  22. Schoenle E., Zapf J., Humbel R. E., Froesch E. R. Insulin-like growth factor I stimulates growth in hypophysectomized rats. Nature. 1982 Mar 18;296(5854):252–253. doi: 10.1038/296252a0. [DOI] [PubMed] [Google Scholar]
  23. Scollay R., Bartlett P., Shortman K. T cell development in the adult murine thymus: changes in the expression of the surface antigens Ly2, L3T4 and B2A2 during development from early precursor cells to emigrants. Immunol Rev. 1984 Dec;82:79–103. doi: 10.1111/j.1600-065x.1984.tb01118.x. [DOI] [PubMed] [Google Scholar]
  24. Tamura K., Kobayashi M., Ishii Y., Tamura T., Hashimoto K., Nakamura S., Niwa M., Zapf J. Primary structure of rat insulin-like growth factor-I and its biological activities. J Biol Chem. 1989 Apr 5;264(10):5616–5621. [PubMed] [Google Scholar]
  25. Tannenbaum G. S. Growth hormone secretory dynamics in streptozotocin diabetes: evidence of a role for endogenous circulating somatostatin. Endocrinology. 1981 Jan;108(1):76–82. doi: 10.1210/endo-108-1-76. [DOI] [PubMed] [Google Scholar]
  26. Weiss A., Imboden J. B. Cell surface molecules and early events involved in human T lymphocyte activation. Adv Immunol. 1987;41:1–38. doi: 10.1016/s0065-2776(08)60029-2. [DOI] [PubMed] [Google Scholar]
  27. Wellhausen S. R. Lymphocyte population dynamics in experimental murine diabetes. Immunol Invest. 1987 Nov;16(7):579–587. doi: 10.3109/08820138709087103. [DOI] [PubMed] [Google Scholar]
  28. Wexler B. C., Lutmer R. F. Adrenal glandular lipids and circulating corticosterone in severely diabetic rats. Br J Exp Pathol. 1975 Aug;56(4):299–306. [PMC free article] [PubMed] [Google Scholar]
  29. Yale J. F., Marliss E. B. Altered immunity and diabetes in the BB rat. Clin Exp Immunol. 1984 Jul;57(1):1–11. [PMC free article] [PubMed] [Google Scholar]
  30. Zapf J., Hauri C., Waldvogel M., Futo E., Häsler H., Binz K., Guler H. P., Schmid C., Froesch E. R. Recombinant human insulin-like growth factor I induces its own specific carrier protein in hypophysectomized and diabetic rats. Proc Natl Acad Sci U S A. 1989 May;86(10):3813–3817. doi: 10.1073/pnas.86.10.3813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. van Vliet E., Melis M., van Ewijk W. The influence of dexamethasone treatment on the lymphoid and stromal composition of the mouse thymus: a flowcytometric and immunohistological analysis. Cell Immunol. 1986 Dec;103(2):229–240. doi: 10.1016/0008-8749(86)90086-9. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES