Abstract
Diabetes mellitus was induced in 40 male C57BL6 mice by injection of a low dose of streptozocin (45 mg/kg body weight) on 5 consecutive days. Twenty four of the mice were immunosuppressed by administration of 1.5 mg FK506/kg body weight daily for 10, 15, 18 and 24 days. Administration of FK506 almost completely inhibited the streptozocin-induced islet damage, and consequently glycaemia remained normal. In FK506-treated animals any inflammatory infiltrate was very sparse and was limited to the vascular pole of the islets. Immunocytochemical results demonstrated that infiltrating cells were Ia-immunoreactive, but were not activated. Ultrastructural observations confirmed the absence of B cell necrosis and degranulation in FK506-treated mice; the few infiltrating elements encountered did not contain phagocytic vesicles or show other signs of activation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bertani T, Perico N, Abbate M, Battaglia C, Remuzzi G (1987) Renal injury induced by long-term administration of cyclosporin A to rats. Am J Pathol 127:569–579
Bluacerraf B, Germain RN (1978) The immune genes of the major histocompatibility complex. Immunol Rev 38:70–119
Carroll PB, Gonçalves AA, Boschero AC, Tzakis AG, Starzl TE, Atwater I (1991) Effect of the immunosuppressant FK506 on insulin release from adult rat islets of Langerhans. Transpl Proc 23:337–339
Dupré J, Stiller CR, Gent M (1988) Effect of immunosuppression with cyclosporine in insulin dependent diabetes mellitus of recent onset: the Canadian open study of 44 months. Transpl Proc 20:184–192
Ericzon B-G, Wijnen RHM, Kubota K, Kootstra G, Groth CG (1991) Effect of FK506 on glucose metabolism in the Cynomolgus monkey: studies in pancreatic transplant recipients and nontransplanted animals. Transpl Proc 23:511
Esposito V, Papaccio G (1988) Nephrotoxicity of cyclosporin A in diabetic BB rats. Micron 19:227–234
Eun HM, Pak CY, Kim CJ, Mc-Arthur RG, Yoon JW (1987) Role of cyclosporin A in macromolecular synthesis of B cells. Diabetes 36:952–958
Ferrero E, Marni A, Ferrero ME, Gaja G, Rugarli C (1985) Effect of cyclosporin A and aminophylline on streptozocin-induced diabetes in rats. Immunol Lett 10:183–187
Hahn HJ, Laube F, Kloting I, Kohmert KD, Warzok R (1986) Toxic effect of cyclosporin A on the endocrine pancreas of Wistar rats. Transplantation 41:44–47
Helmchen U, Schmidt WE, Siegel EG, Creutzfeldt W (1984) Morphological and functional changes of pancreatic beta cells in cyclosporin A treated rats. Diabetologia 27:416–418
Honbo T, Kobayashi M, Hane K, Hata T, Ueda Y (1987) The oral dosage form of FK506. Transpl Proc [Suppl 6] 19:17–22
Jenner M, Bradish G, Stiller C, Atkinson P for the London Diabetes Study Group (1992) Cyclosporin A treatment for young children with newly-diagnosed type 1 (insulin-dependent) diabetes mellitus. Diabetologia 35:884–888
Kai N, Motojima K, Tsunoda T, Kanematsu T (1993) Prevention of insulitis and diabetes in nonobese diabetic mice by administration of FK506. Transplantation 55:936–940
Kino T, Hatanaka H, Miyata S, Inamura N, Nishiyama M, Yajima T, Goto T, Okahara M, Kohsaka M, Aoki N, Ochiai T (1987) FK506, a novel immunosuppressant isolated from a Streptomyces. II immunosuppressive effect of FK506 in vitro. J Antibiotics 40:1256–1265
Kolb-Bachofen V, Epstein S, Kiesel U, Kolb H (1988) Low dose streptozocin-induced diabetes in mice. Electron microscopy reveals single cell insulitis before diabetes onset. Diabetes 37:21–27
Like AA, Rossini AA (1976) Streptozotocin induced pancreatic insulitis: a new model of diabetes mellitus. Science 193:415–417
Malorny U, Knop J, Burmeister G, Sorg C (1988) Immunohistochemical demonstration of migration inhibiting factor (MIF) in experimental allergic contact dermatitis. Clin Exp Immunol 71:164–170
Murase N, Todo S, Lee PH, Lai H, Chapamn F, Nalesnik MA, Makowka L, Starzl TE (1987) Heterotopic heart tranplantation in the rat under FK506 alone or with cyclosporin. Transpl Proc 19 [Suppl 6]:71–75
Murase N, Lieberman I, Nalesnik MA, Mintz DH, Todo S, Drash AL, Starzl TE (1990) Effect of FK506 on spontaneous diabetes in BB rats. Diabetes 39:1584–1586
Papaccio G (1993) Gangliosides prevent insulitis but not islet B cell destruction in low dose streptozocin treated mice. Diabetes Res Clin Pr 19:9–15
Papaccio G, Esposito V (1990) Cyclosporin administration during pregnancy induces ultrastructural changes on pancreatic beta cells of newborn rats. Acta Anat 137:336–341
Papaccio G, Esposito V (1992) Ultrastructural observations on cytotoxic effector cells infiltrating pancreatic islets of low dose streptozocin treated mice. Virchows Archiv [A] 420:5–10
Papaccio G, Esposito V, Mezzogiorno V (1989) Multiple low dose streptozocin treated rats: biochemical and morphological effects of cyclosporin A administration. Cell Mol Biol 35:409–420
Papaccio G, Linn T, Federlin K, Volkman A, Esposito V, Mezzogiorno V (1991) Further morphological and biochemical observations on early low dose streptozocin diabetes in mice. Pancreas 6:659–667
Papaccio G, Chieffi Baccari G, Esposito V (1992) Immunomodulation of low dose streptozocin diabetes in mice reveals that insulitis is not obligatory for B cell destruction. J Anat 18:403–408
Papaccio G, Linn T, Chieffi Baccari G (1993) Morphological observations on islet blood vessels of low dose streptozocin treated mice. J Anat 182:45–54
Ricordi C, Zeng Y, Alejandro R, Tzakis A, Venkataramanan R, Fung J, Breiter D, Mintz DH, Starzl TE (1991) In vivo effect of FK506 on human pancreatic islets. Transplantation 52:519–522
Sabbatini M, De Nicola L, Uccello F, Romano G, Papaccio G, Esposito V, Sepe V, Conte G, Fuiano G (1991) Medium-term cyclosporin renal dysfunction and its reversibility in rats. Am J Physiol 260:898–905
Starzl TE, Todo S, Fung J, Demetris AJ, Venkataramanan R, Jain A (1989) FK506 for human liver, kidney and pancreas transplantation. Lancet II:1000–1004
Todo S, Fung J, Starzl TE, Tzakis A, Demetris AJ, Kormos R, Jain A, Alessiani M, Takaya S (1990) Liver, Kidney and thoracic organ transplantation under FK506. Ann Surg 212:295–305
Yasunami Y, Ryu S, Kamei T (1990) Characterization of the immunosuppressive activity of FK506 in rat islet allografts. Transpl Proc 22:875
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Papaccio, G., Latronico, M. & Baccari, G.C. The immunosuppressant FK506 inhibits the damage to mouse pancreatic islets induced by low dose streptozocin. Cell Tissue Res 277, 573–578 (1994). https://doi.org/10.1007/BF00300231
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00300231