Endocrine Pathology

, Volume 17, Issue 3, pp 283–290 | Cite as

Lymphocytic insulitis in a juvenile dog with diabetes mellitus

  • G. Jouvion
  • J. Abadie
  • J. M. Bach
  • F. Roux
  • J. Miclard
  • J. Y. Deschamps
  • L. Guigand
  • P. Saï
  • M. Wyers
Animal Model

Abstract

Autoimmune diabetes has never been described in a juvenile dog, whereas serologica evidence has established its development in adult dogs. Diabetes mellitus was diagnosea in a 3-mo-old Donge de Bordeaux dog suffering from persistent hyperglycemia and concurrent insulinopenia. Histological analysis of the pancreas revealed in flammatory lesions in 40% of the islets of Lagerhans, with infiltration predominantly by T lymphocytes (more than 90%), either at the edge (peri-insulitis: 10%) or in the islets (insulitis: 30%). The remaining 60% of the islets showed a marked atrophy due to massive beta cell loss with no loss of alpha cells. This pattern is quite similar to that observed in humans in which a characteristic insulitis containing high numbers of T lymphocytes is found in 20% of the islets at diabetes diagnosis. By contrast, in rodent models, nearly 70% of the islets of langerhans show inflamation at diagnosis and macrophages and dendritic cells predominate in the inflamatory lesions. This is the first report of lymphocytic insulitis in a juvenile dog exhibiting diabetes mellitus. Our observations suggest an autoimmune origin for the disease in this dog that is similar to human type 1 diabetes mellitus, for which there is no accurate spontaneous large animal model.

Key words

Autoimmune disease diabetes mellitus dog juvenile onset lymphocytic insulitis 

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References

  1. 1.
    American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 29(Suppl 1): S43–48, 2006.Google Scholar
  2. 2.
    Maitra A, Abbas AK, The endocrine pancreas In: Kumar V, Abbas AK, Fausto N, eds. Robbins and Cotran pathologic basis of disease. Philadelphia, PA: Elsevier, 2005; 1189–1207.Google Scholar
  3. 3.
    Catchpole B, Ristic JM, Fleeman LM, Davison LJ, Canine diabetes mellitus: can old dogs teach us new tricks? Diabetologia 48:1948–1956, 2005.PubMedCrossRefGoogle Scholar
  4. 4.
    Miller BJ, Appel MC, O'Neil JJ, Wicker I. S. Both the Lyt-2+ and L3T4+T cell subsets are required for the transfer of diabetes in nonobese diabetic mice. J Immunol 140:52–58, 1988.PubMedGoogle Scholar
  5. 5.
    Bottazzo GF, Dean BM, McNally JM, MacKay EH, Swift PG, Gamble DR In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. N Engl J Med 313:353–360, 1985.PubMedCrossRefGoogle Scholar
  6. 6.
    Atkins CE, Hill JR, Johnson RK. Diabetes mellitus in the juvenile dog: a report of four cases. J Am Vet Met Assoc 175:362–368. 1979.Google Scholar
  7. 7.
    Atkins CE, LeCompte PM, Chin HP, Hill JR, Ownby CL, Brownfield MS. Morphologic and immunocytochemical study of young dogs with diabetes mellitus associated with pancreatic isler hypoplasia. Am J Vet Res 49:1577–1581 1988.PubMedGoogle Scholar
  8. 8.
    Elie M, Hoenig M, Canine immune-mediated diabetes mellitus: a case report. J Am Anim Hosp Assoc 31:295–299, 1995.PubMedGoogle Scholar
  9. 9.
    Gale EA, Do dogs develop autoimmune diabetes. Diabetologia 48:1945–1947, 2005.PubMedCrossRefGoogle Scholar
  10. 10.
    Gale EA. The discovery of type 1 diabetes Diabetes 50:217–226, 2001.PubMedCrossRefGoogle Scholar
  11. 11.
    Gepts W, Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes 14:619–633, 1965.PubMedGoogle Scholar
  12. 12.
    Bottazzo GF, Florin-Christensen A, Doniach D. Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancer 2:1279–1283, 1974.CrossRefGoogle Scholar
  13. 13.
    Lendrum R, Walker G, Cudworth AG, et al. Islet-cell antibodies in diabetes mellitus. Lancet 2:1273–1276, 1976.PubMedCrossRefGoogle Scholar
  14. 14.
    Palmer JP, Asplin CM, Clemons P, et al. Insulin antibodies in insulin-dependent diabetics before insulin treatment. Science 222: 1337–1339. 1983.PubMedCrossRefGoogle Scholar
  15. 15.
    Verge CF, Stenger D, Bonifacio E, et al. Combined use of autoantibodies (IA-2) autoantibody, GAD autoantibody, insu in autoantibody, cytoplasmic islet cell antibod ies) in type 1 diabetes: Combinatorial Islet Autoantibody Workshop. Diabetes 47:1857–1866, 1998.PubMedCrossRefGoogle Scholar
  16. 16.
    Yu L, Robles DT, Abiru N, et al. Early expression of antiinsulin autoantibodies of humans and the NOD mouse: evidence for early determination of subsequent diabetes. Proc Natl Acad Sci USA 97:1701–1706, 2000.PubMedCrossRefGoogle Scholar
  17. 17.
    Haines DM, Penhale WJ Autoantibodies to pancreatic islet cells in canine diabetes mellitus. Vet Immunol Immunopathol 8:149–156, 1985.PubMedCrossRefGoogle Scholar
  18. 18.
    Haines DM. A re-examination of islet cell cytoplasmic antibodies in diabetic dogs. Vet Immunol Immunopathol 11:225–233, 1986.PubMedCrossRefGoogle Scholar
  19. 19.
    Davison LJ, Ristic JM, Herrtage ME, Ramsey IK, Catchpole B. Anti-insulin antibodies in dogs with naturally occurring diabetes mellitus. Vet Immunol Immunopathol 91:53–60, 2003.PubMedCrossRefGoogle Scholar
  20. 20.
    Sai P, Debray-Sachs, M, Jondet A, Gepts W, Assan R. Anti-beta-cell immunity in insulinopenic diabetic dogs. Diabetes 33:135–140, 1984.PubMedCrossRefGoogle Scholar
  21. 21.
    Kimmel SE, Ward CR, Henthorn PS, Hess RS. Familial insulin-dependent diabetes mellitus in Samoyed dogs. J Am Anim Hosp Assoc 38:235–238, 2002.PubMedGoogle Scholar
  22. 22.
    Kramer JW, Nottingham S, Robinette J, Lenz G, Sylvester S, Dessouly MI. Inherited, early onset, insulin-requiring diabetes melliutus of Keeshond dogs. Diabetes 29:558–565, 1980.PubMedCrossRefGoogle Scholar
  23. 23.
    Alejandro R, Feldman EC, Shienvold FL, Mintz DH. Advances in canine diabetes mellitus research: etiopathology and results of islet transplantation. J Am Vet Med Assoc 193:1050–1155, 1988.PubMedGoogle Scholar
  24. 24.
    Minkus G, Breuer W, Arun S, et al. Ductuloendocrine cell proliferation in the pancreas of two young dogs with diabetes mellitus. Vet Pathol 34:164–167, 1997.PubMedCrossRefGoogle Scholar
  25. 25.
    Gepts W, Toussaint D. Spontaneous diabetes in dogs and cats. A pathological study. Diabetologia 3:249–265, 1967.PubMedCrossRefGoogle Scholar
  26. 26.
    Atkins CE, Chin HP. Insulin kinetics in juvenile canine diabetics after glucose loading. Am J Vet Res 44:596–600, 1983.PubMedGoogle Scholar
  27. 27.
    Rosmalen JG, Martin T, Dobbs C, et al. Subsets of macrophages and dendritic cells in nonobese diabetic mouse pancreatic infammatory infiltrates: correlation with the development of diabetes. Lab Invest 80:23–30, 2000.PubMedCrossRefGoogle Scholar
  28. 28.
    Voorbij HA, Jeucken PH, Kabel PJ, De Haan M, Drexhage HA, Dendritic cells and scavenger macrophages in pancreatic islets of prediabetic BB rats. Diabetes 38:1623–1629, 1989.PubMedCrossRefGoogle Scholar
  29. 29.
    Reddy S, Liu W, Elliott RB. Distribution of pancreatic macrophages preceding and during early insulitis in young NOD mice. Pancreas 8:602–608, 1993.PubMedCrossRefGoogle Scholar
  30. 30.
    Foulis AK, Stewart JA. The pancreas in recentonset type 1 (insulin-dependent) diabetes mellitus: insulin content of islets, insulitis and associated changes in the exocrine acinar tissue. Diabetologia 26:456–461, 1984.PubMedCrossRefGoogle Scholar
  31. 31.
    Hanafusa T, Miyazaki A, Miyagawa J, et al. Examination of islets in the pancreas biopsy specimens from newly diagnosed type 1 (insulin-dependent) diabetic patients. Diabetologia 33:105–111, 1990.PubMedCrossRefGoogle Scholar
  32. 32.
    Mueller R, Krahl T, Sarvetnick N. Pancreatic expression of interleukin-4 abrogates insulitis and autoimmune diabetes in nonobese diabetic (NOD) mice. J Exp Med 184:1093–1099 1996.PubMedCrossRefGoogle Scholar
  33. 33.
    Sai P, Gouin E. [Spontaneous animal models for insulin-dependent diabetes (type 1 diabetes)]. Vet Res 28:223–229, 1997.PubMedGoogle Scholar

Copyright information

© Humana Press Inc 2006

Authors and Affiliations

  • G. Jouvion
    • 1
  • J. Abadie
    • 1
  • J. M. Bach
    • 2
  • F. Roux
    • 2
    • 3
  • J. Miclard
    • 1
  • J. Y. Deschamps
    • 2
    • 3
  • L. Guigand
    • 1
  • P. Saï
    • 2
  • M. Wyers
    • 1
  1. 1.UMR 703 INRA-ENVN, Department of PathologyNational Veterinary School of NautesFrance
  2. 2.IECM Unit, INRA U707University, National Veterinary School of NantesFrance
  3. 3.Eniergency and Critical Care UnitNational Veterinary School of NantesFrance

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