Viral Pathogenesis of Insulin-Dependent Diabetes Mellitus

  • Ji-Won Yoon
Part of the Endocrinology and Metabolism book series (EAM, volume 4)


The familial occurrence of diabetes, or at least, a tendency to develop the disease, has been long recognized, but the true nature of the genetic mechanisms governing transmission of the diabetes trait still is not well understood. Concordance for insulin-dependent diabetes mellitus (IDDM) between identical twins approaches 50%, suggesting that nongenetic influences, such as environmental factors, contribute to the clinical expression of a genetic susceptibility. Triggering factors that might induce diabetes include diabetogenic viruses, chemicals, diet, and toxins. Such likely candidates act either as primary injurious agents to pancreatic beta-cells or as triggers of autoimmunity in man and animals (Fig. 10.1).1,2


Viral Antigen Rubella Virus Viral Pathogenesis Coxsackie Virus Encephalomyocarditis Virus 
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  1. 1.
    Yoon JW, Kim CJ, Pak CY, McArthur RG. Environmental factors and IDDM. Clin Invest Med1987; 1457 – 469.Google Scholar
  2. 2.
    Leiter EH, Wilson GL. Viral interactions with pancreatic beta cells, in Lefebvre PJ, Pipeleers DG (eds): The Pathology of the Endocrine Pancreas in Diabetes. New York: Springer-Verlag, 1988, pp 85 – 105.Google Scholar
  3. 3.
    Yoon JW, Notkins AL. Virus-induced diabetes mellitus in mice. Metabolism1983; 32 (Suppl): 37 – 40.PubMedCrossRefGoogle Scholar
  4. 4.
    Notkins AL, Yoon JW, Onodera T, Toniolo T, Janson AB. Virus-induced diabetes mellitus. Perspect Virol1981; 11: 141 – 62.Google Scholar
  5. 5.
    Craighead JE. The role of viruses in the pathogenesis of pancreatic diseases and diabetes mellitus. Prog Med Virol1975; 19: 161 – 214.PubMedGoogle Scholar
  6. 6.
    Yoon JW, Austin M, Onodera T, Notkins AL. Virus-induced diabetes mellitus. Isolation of a virus from the pancreas of a child with diabetic ketoacidosis. N Engl J Med1979; 300: 1173 – 1179.PubMedCrossRefGoogle Scholar
  7. 7.
    Champsaur H, Bottazzo G, Bertrams J, Assan R, Bach C. Virologic, immunologic and genetic factors in insulin-dependent diabetes mellitus. J Pediatr1982; 100: 15 – 20.PubMedCrossRefGoogle Scholar
  8. 8.
    King ML, Shaikh A, Bidwell B, Voller A, Banatvala JE. Coxsackie-B-virus specific IgM responses in children with insulin-dependent diabetes mellitus. Lancet 1983; i:1397–1399.CrossRefGoogle Scholar
  9. 9.
    Banatvala JE, Schemthaner G, Schober E, et al. Coxsackie B, mumps, rubella and cytomegalovirus specific IgM responses in patients with juvenile-onset insulin-dependent diabetes mellitus in Britain, Austria and Australia. Lancet 1985; i:1409–1412.CrossRefGoogle Scholar
  10. 10.
    Rubinstein P, Walker ME, Fedun B, Witt ME, Cooper LZ, Ginsberg-Fellner F. The HLA system in congenital rubella patients with and without diabetes. Diabetes1982; 31: 1088 – 1091.PubMedCrossRefGoogle Scholar
  11. 11.
    Pak CY, Eun HM, McArthur RG, Yoon JW. Association of cytomegalovirus infection with autoimmune type I diabetes. Lancet 1988; ii:l–4.CrossRefGoogle Scholar
  12. 12.
    Jenson AB, Rosenberg HS, Notkins AL. Pancreatic islet cell damage in children with fatal viral infections. Lancet1980; 2: 354 – 358.PubMedGoogle Scholar
  13. 13.
    Craighead JE, McLane MF. Diabetes mellitus: Induction in mice by encephalomyocarditis virus. Science1968; 162: 913 – 915.PubMedCrossRefGoogle Scholar
  14. 14.
    Yoon JW, McClintock PR, Onodera T, Notkins AL. Virus-induced diabetes mellitus. Inhibition by a non-diabetogenic variant of encephalomyocarditis virus. J Exp Med1980; 152: 878 – 892.PubMedCrossRefGoogle Scholar
  15. 15.
    Suenaga K, Yoon JW. Association of beta cell specific expression of endogenous retrovirus with the development of insulitis and diabetes in NOD mice. Diabetes1988; 37: 1722 – 1726.PubMedCrossRefGoogle Scholar
  16. 16.
    Yoon JW, Morishima T, McClintock PR, Austin M, Notkins AL. Virus-induced diabetes mellitus: Mengovirus infects pancreatic beta cells in strains of mice resistant to the diabetogenic effect of encephalomyocarditis mice. J Virol1984; 50: 684 – 690.PubMedGoogle Scholar
  17. 17.
    Yoon JW, Onodera T, Notkins AL. Virus-induced diabetes mellitus: Beta cell damage and insulin-dependent hyperglycemia in mice infected with Coxsackie virus B4. J Exp Med1978; 148: 1068 – 1080.PubMedCrossRefGoogle Scholar
  18. 18.
    Yoon JW, McClintock PR, Bachurski LJ, Longstretch JD, Notkins AL. Virus-induced diabetes. No evidence for immune mechanisms in the destruction of beta cells by encephalomyocarditis virus. Diabetes1985; 34: 922 – 925.PubMedCrossRefGoogle Scholar
  19. 19.
    Onodera T, Yoon JW, Brown KS, Notkins AL. Evidence for a single locus controlling susceptibility to virus-induced diabetes mellitus. Nature1978; 274: 693 – 695.PubMedCrossRefGoogle Scholar
  20. 20.
    Yoon JW, Notkins AL. Virus-induced diabetes mellitus VI. Genetically determined host differences in the replication of encephalomyocarditis virus in pancreatic beta cells. J Exp Med1976; 143: 170 – 185.CrossRefGoogle Scholar
  21. 21.
    Chairez R, Yoon JW, Notkins AL. Virus-induced diabetes mellitus. X. Attachment of encephalomyocarditis virus and permissiveness of cultured pancreatic beta cells to infection. Virology1978; 85: 606 – 611.PubMedCrossRefGoogle Scholar
  22. 22.
    Yoon JW, Lesniak MA, Fussganger R, Notkins AL. Genetic differences in the susceptibility of pancreatic B cells to virus-induced diabetes mellitus. Nature1976; 265: 178 – 180.CrossRefGoogle Scholar
  23. 23.
    Jansen FK, Miiterfering H, Schmidt WAK. Virus-induced diabetes and the immune system: Suggestion that appearance of diabetes depends on immune reactions. Diabetologia1977; 13: 545 – 549.PubMedCrossRefGoogle Scholar
  24. 24.
    Jansen FK, Turnoyssen O, Miinterfering H. Virus-induced diabetes and the immune system. I. Evidence for an immunopathogenesis of the acute phase of diabetes. Biomedicine1979; 31: 1 – 2.PubMedGoogle Scholar
  25. 25.
    Buschard K, Rygaard J, Lund E. The inability of a diabetogenic virus to induce diabetes mellitus in athymic (nude) mice. Acta Pathol Microbiol Scand1976; C84: 299 – 303.Google Scholar
  26. 26.
    Buschard K, Hastrup N, Rygaard J. Virus-induced diabetes mellitus in mice and the thymus-dependent immune system. Diabetologia1983; 24: 42 – 46.PubMedCrossRefGoogle Scholar
  27. 27.
    Vialettes B, Baume D, Charpin C, De Maeyer-Guignard J, Vague P. Assessment of viral and immune factors in EMC virus-induced diabetes: Effects of cyclosporin A and interferon. J Clin Lab Immunol1983; 10: 35 – 40.PubMedGoogle Scholar
  28. 28.
    Notkins AL, Yoon JW. Virus-induced diabetes in mice prevented by a live attenuated vaccine. N Engl J Med1982; 306: 486.PubMedGoogle Scholar
  29. 29.
    Babu PG, Huber SA, Craighead JE. Contrasting features of T lymphocyte mediated diabetes in encephalomyocarditis virus infected Balb/c By and Balb/c Cum mice. Am J Pathol1986; 124: 193 – 198.PubMedGoogle Scholar
  30. 30.
    Haynes MK, Huber SA, Craighead JE. Helper-induced T-lymphocyte mediated diabetes in EMC-infected Balb/c ByJ mice. Diabetes1987; 36: 877 – 881.PubMedCrossRefGoogle Scholar
  31. 31.
    Ross ME, Onodera T, Brown KS, Notkins AL. Virus-induced diabetes mellitus. IV. Genetic and environmental factors influencing the development of diabetes after infection with the M variant of encephalomyocarditis virus. Diabetes1976; 25: 190 – 197.PubMedCrossRefGoogle Scholar
  32. 32.
    Yoon JW, Onodera T, Notkins AL. Virus induced diabetes mellitus. Passage of encephalomyocarditis virus and severity of diabetes in susceptible and resistant strains of mice. J Gen Virol1977; 37: 225 – 232.PubMedCrossRefGoogle Scholar
  33. 33.
    Yoon JW. Viruses and the pathogenesis of insulin-dependent diabetes mellitus, in Genetic Environmental Interaction in Diabetes Mellitus (ed. John S. Melish, J. Hanna and S. Baba) Excerpta Medica, Amsterdam-Oxford-Princeton International Congress Series 1982;549:227–34.Google Scholar
  34. 34.
    Yoon JW, Cha CY, Jordan G. Role of interferon in virus-induced diabetes in mice. J Infect Dis1983; 147: 155 – 159.PubMedCrossRefGoogle Scholar
  35. 35.
    Ray U, Aulakh G, McClintock PR, Yoon JW, Notkins AL. Virus-induced diabetes mellitus: Difference in the RNA fingerprints of diabetogenic and nondiabetogenic variants of encephalomyocarditis virus. J Gen Virol1983; 64: 947 – 950.PubMedCrossRefGoogle Scholar
  36. 36.
    Yoon JW, Wong AKC, Bae YS, Eun HM. An apparent deletion of an oligonucleotide detected by RNA fingerprint in the nondiabetogenic B variant of encephalomyocarditis virus is due to a point mutation. J Virol1988; 62: 637 – 640.PubMedGoogle Scholar
  37. 37.
    Jordan GW, Cohen SH, Dandekar S, Vande-Brink KM. The genomic RNA of diabetogenic encephalomyocarditis virus: Characterization and molecular cloning. Virology1987; 159: 120 – 125.PubMedCrossRefGoogle Scholar
  38. 38.
    Yoon JW, Ko W, Bae YS, Pak CY, Amano K, Eun HM, Kim MK. Identification of antigenic differences between the diabetogenic and nondiabetogenic variants of encephalomyocarditis virus by monoclonal antibodies. J Gen Virol1988; 69: 1085 – 1090.PubMedCrossRefGoogle Scholar
  39. 39.
    Eun HM, Bae YS, Yoon JW. Amino acid differences in capsid protein, VP1, between diabetogenic and nondiabetogenic variants of encephalomyocarditis virus. Virology1988; 163: 369 – 373.PubMedCrossRefGoogle Scholar
  40. 40.
    Bae YS, Eun HM, Yoon JW. Molecular identification of diabetogenic viral gene. Diabetes1989; 38: 316 – 320.PubMedCrossRefGoogle Scholar
  41. 41.
    Yoon JW, Rodrigues MM, Currier C, Notkins AL. Long-term complications of virus-induced diabetes in mice. Nature1982; 296: 567 – 569.CrossRefGoogle Scholar
  42. 42.
    Rodrigues M, Currier C, Yoon JW. Electron microscopy of renal and ocular changes in virus-induced diabetes mellitus in mice. Diabetologia1983; 24: 293 – 299.PubMedCrossRefGoogle Scholar
  43. 43.
    Yoon JW, Reddi AH. Decreased bone formation and mineralization in virus-induced diabetes mellitus. Am J Physiol1984; 246: C177 – C179.PubMedGoogle Scholar
  44. 44.
    Morishima T, McClintock PR, Billups LC, Notkins AL. Expression and modulation of virus receptors on lymphoid and myeloid cells: Relationship to infectivity. Virology1982; 116: 605 – 618.PubMedCrossRefGoogle Scholar
  45. 45.
    Toniolo A, Onodera T, Jordan G, Yoon JW, Notkins AL. Virus-induced diabetes mellitus: Glucose abnormalities produced in mice by the six members of the Coxsackie B virus group. Diabetes1982; 31: 496 – 499.PubMedCrossRefGoogle Scholar
  46. 46.
    Ross ME, Hayashi K, Notkins AL. Virus-induced pancreatic disease: Alterations in concentration of glucose and amylase in blood. J Infect Dis1974; 129: 669 – 676.PubMedCrossRefGoogle Scholar
  47. 47.
    Toniolo A, Onodera T, Yoon JW, Notkins AL. Induction of diabetes by cumulative environmental insults from viruses and chemicals. Nature1980; 288: 383 – 385.PubMedCrossRefGoogle Scholar
  48. 48.
    Wegner U, Kewitsch A, Madauss M, Dohner L, Zuhlke H. Hyperglycemia in BALB/c mice after pretreatment with one subdiabetogenic dose of streptozotocin and subsequent infection with Coxsackie B4 strain. Biomed Biochem Acta1985; 44: 21 – 27.Google Scholar
  49. 49.
    Yoon JW, London WT, Curfman BL, Brown RL, Notkins AL. Coxsackie virus B4 produces transient diabetes in nonhuman primates. Diabetes1986; 35: 712 – 716.PubMedCrossRefGoogle Scholar
  50. 50.
    Prabhakar BS, Haspel MV, McClintock PR, Notkins AL. High frequency of antigenic variants among naturally occurring human Coxsackie B4 virus isolates identified by monoclonal antibodies. Nature1982; 300: 374 – 376.PubMedCrossRefGoogle Scholar
  51. 51.
    Prabhakar BS, Menegus MA, Notkins AL. Detection of conserved and nonconserved epitopes on Coxsackie virus B4: Frequency of antigenic change. Virology1985; 146: 302 – 306.PubMedCrossRefGoogle Scholar
  52. 52.
    Gamble DR, Kinsley ML, Fitzgerald MG, Bolton R, Taylor KW. Viral antibodies in diabetes mellitus. Br Med J1969; 3: 627 – 630.PubMedCrossRefGoogle Scholar
  53. 53.
    Hierholzer JC, Farris WA. Follow-up of children infected in a Coxsackie B3 and B4 outbreak: No evidence of diabetes. J Infect Dis1974; 129: 741 – 746.PubMedCrossRefGoogle Scholar
  54. 54.
    Dippe SE, Bennet PH, Miller M. Coxsackie B virus and diabetes. Br Med J1974; 2: 443 – 444.PubMedCrossRefGoogle Scholar
  55. 55.
    Friman G, Fohlman J, Frisk G, Diderholm H, Ewald U, Kobbah M, Tuvemo T. An incidence peak of juvenile diabetes. Relation to Coxsackie B virus immune response. Acta Peadiatr Scand1985; 320 (Suppl): 14 – 19.CrossRefGoogle Scholar
  56. 56.
    Prince G, Jenson AB, Billups L, Notkins AL. Infection of human pancreatic beta cell cultures with mumps virus. Nature1978; 271: 158 – 161.PubMedCrossRefGoogle Scholar
  57. 57.
    Yoon JW, Onodera T, Notkins AL. Virus-induced diabetes mellitus. XI. Replication of Coxsackie virus B3 in human pancreatic beta cell cultures. Diabetes1978; 27: 778 – 782.PubMedCrossRefGoogle Scholar
  58. 58.
    Yoon JW, Selvaggio S, Onodera T, Wheeler J, Jenson AB. Infection of cultured human pancreatic B cell with reovirus type 3. Diabetologia1981; 20: 462 – 468.PubMedCrossRefGoogle Scholar
  59. 59.
    McLaren LC, Holland JJ, Syverton JT. The mammalian cell-virus relationship. J Exp Med1959; 109: 475 – 483.PubMedCrossRefGoogle Scholar
  60. 60.
    Gladisch R, Hofmann W, Waldherr R. Myocarditis and insulitis in Coxsackie virus infection. Z Kardiol1976; 65: 873 – 881.Google Scholar
  61. 61.
    Eisenbarth GS. Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med1986; 314: 1360 – 1368.PubMedCrossRefGoogle Scholar
  62. 62.
    Foulis AK, Farquharsaon MA, Meager A. Immunoreactive a-interferon in insulin-secreting B cells in type I diabetes mellitus. Lancet 1987; ii:1423–1427.CrossRefGoogle Scholar
  63. 63.
    Rayfield EJ, Kelly KJ, Yoon JW. Rubella virus-induced diabetes in hamsters. Diabetes1986; 35: 1278 – 1281.PubMedCrossRefGoogle Scholar
  64. 64.
    Onodera T, Toniolo A, Ray UR, Jenson AB, Knazek RA, Notkins AL. Virus-induced diabetes mellitus. J Exp Med1981; 153: 1457 – 1465.PubMedCrossRefGoogle Scholar
  65. 65.
    Onodera T, Ray UR, Melez KA, Suzuki H, Toniolo A, Notkins AL. Virus-induced diabetes mellitus. Autoimmunity and polyendocrine disease prevented by immunosuppression. Nature1982; 297: 66 – 69.PubMedCrossRefGoogle Scholar
  66. 66.
    Schlesinger MJ, Kaarianen L. Translation and processing of alpha virus proteins, in, Schlesinger RW (ed): Togavirus. New York: Academic Press, 1980, pp 371 – 389.Google Scholar
  67. 67.
    Allison AC. Mechanisms by which autoimmunity can be produced, in Mendel NE, Cheers C, Hoskins CS, McKenzie IFC, Nossal H (eds): Progress in Immunology, vol. III. Amsterdam: Elsevier, 1977, p 512.Google Scholar
  68. 68.
    Fauci AC. Immunoregulation of autoimmunity. J Allergy Clin Immunol1980; 66: 5 – 17.PubMedCrossRefGoogle Scholar
  69. 69.
    Reinherz EL, Schlossman SF. Regulation of the immune response inducer and suppressor T-lymphocytes subsets in human beings. N Engl J Med1980; 303: 370 – 373.PubMedCrossRefGoogle Scholar
  70. 70.
    Kataoka S, Satoh J, Fujiya H, Toyota T, Suzuki R, Itoh K, Kumagai K. Immunologic aspects of the nonobese diabetes (NOD) mouse: Abnormalities of cellular immunity. Diabetes1983; 32: 247 – 253.PubMedCrossRefGoogle Scholar
  71. 71.
    Lee KU, Amano K, Yoon JW. Evidence for initial involvement of macrophage in development of insulitis in NOD mice. Diabetes1988; 37: 989 – 991.PubMedCrossRefGoogle Scholar
  72. 72.
    Harada M, Makino S. Promotion of spontaneous diabetes in nonobese diabetes-prone mice by cyclophosphamide. Diabetologia1982; 27: 604 – 606.CrossRefGoogle Scholar
  73. 73.
    Harada M, Sueishi T, Misaki R, Makino S. Possible role of Lyt 2+ T cells in cyclophosphamide-enhanced diabetes in NOD mice. Presented at the International Research Symposium “The Immunology of Diabetes,” Oct 27–30, Woods Hole, MA, 1987.Google Scholar
  74. 74.
    Ikeda H, Pincus T, Yoshiki T, Strand M, August JT, Boyse EA, Mellors RC. Biological expression of antigenic determinants of murine leukemia virus proteins gp 69/71 and p 30. J Virol1974; 14: 1274 – 1280.PubMedGoogle Scholar
  75. 75.
    Del Villano BC, Nave B, Croker BP. The oncornavirus glycoprotein gp 69/71: A constituent of the surface of normal and malignant thymocytes. J Exp Med1975; 141: 172 – 187.CrossRefGoogle Scholar
  76. 76.
    Kennel SJ, Feldman JD. Distribution of viral glycoprotein gp 69/71 on cell surfaces of producer and nonproducer cells. Cancer Res1976; 36: 200 – 208.PubMedGoogle Scholar
  77. 77.
    Lerner RA, Wilson CB, Del Villano BC, McCohahey PJ, Dixon FJ. Endogenous oncornaviral gene expression in adult and fetal mice: Quantitative, histologic, and physiologic studies of the major viral glycoprotein, gp 70. J Exp Med1976; 143: 151 – 166.PubMedCrossRefGoogle Scholar
  78. 78.
    Unanue ER, Allen PM. The basis for the immunoregulatory role of macrophages and other accessory cells. Science1987; 236: 551 – 557.PubMedCrossRefGoogle Scholar
  79. 79.
    Toews GB, Bergstresser PR, Streilein JW. Epidermal Langerhans cell density determines whether contact hypersensitivity or unresponsiveness follows skin painting with DNFB. J Immunol1980; 124: 445 – 453.PubMedGoogle Scholar
  80. 80.
    Onodera T, Jenson AB, Yoon JW, Notkins AL. Virus-induced diabetes mellitus. Reovirus infection of pancreatic beta cells in mice. 1978; 301: 529 – 531.Google Scholar
  81. 81.
    Menser MA, Forrest JM, Bransby RD. Rubella infection and diabetes mellitus. Lancet 1978; i:57–60.CrossRefGoogle Scholar
  82. 82.
    Schopfer K, Matter L, Flueler U, Werder E, Diabetes mellitus, endocrine autoantibodies and prenatal rubella infection. Lancet 1982; ii:159.CrossRefGoogle Scholar
  83. 83.
    Underwood LE, Van Wyk J J. Hormones in normal and aberrant growth, in Williams RH (ed): Textbook of Endocrinology( 6th ed ). Philadelphia: Saunders, 1981, pp 1149 – 1184.Google Scholar
  84. 84.
    Preece MA, Kearney PJ, Marshall WC. Growth-hormone deficiency in congenital rubella. Lancet 1977; ii:842–844.CrossRefGoogle Scholar
  85. 85.
    Smithsells RW, Sheppard S, Marshall WC, Peckham C. Congenital rubella and diabetes mellitus. Lancet 1978; i:439.CrossRefGoogle Scholar
  86. 86.
    DePrins F, VanAssche FA, Desmyter J. Congenital rubella and diabetes mellitus. Lancet 1978; i:439–440.Google Scholar
  87. 87.
    Patterson K, Chandra RS, Jenson AB. Congenital rubella, insulitis and diabetes mellitus in an infant. Lancet 1981; i:1048–1049.CrossRefGoogle Scholar
  88. 88.
    Ginsberg-Fellner F, Witt ME, Yagihashi S, et al. Congenital rubella syndrome as a model for type I (insulin-dependent) diabetes mellitus: Increased prevalence of islet cell surface antibodies. Diabetologia1984; 27: 87 – 89.PubMedCrossRefGoogle Scholar
  89. 89.
    Ginsberg-Fellner F, Witt ME, Fedun B, et al. Diabetes mellitus and autoimmunity in patients with congenital rubella syndrome. Rev Infect Dis1985; 7 (Suppl 1): S170 – S175.PubMedCrossRefGoogle Scholar
  90. 90.
    Ginsberg-Fellner F, Fedun B, Cooper Z, et al. Interrelationships of congenital rubella and type I insulin dependent diabetes mellitus, in Jaworski JA, Molnar GD, Rajotte RV, Singh B (eds): The Immunology of Diabetes Mellitus. Amsterdam: Elsevier, 1987, pp 279 – 286.Google Scholar
  91. 91.
    Ward KP, Galloway WH, Auchterlonie IA. Congenital cytomegalovirus infection and diabetes. Lancet 1979; i:497.CrossRefGoogle Scholar
  92. 92.
    Fox GJ, Murphy JC. Cytomegalic virus-associated insulitis in diabetic Octodon degus. Vet Pathol1979; 16: 625 – 628.CrossRefGoogle Scholar
  93. 93.
    Helmke K, Otten A, Willems W. Islet cell antibodies in children with mumps infection. Lancet 1980; ii:211–212.CrossRefGoogle Scholar
  94. 94.
    Gamble DR. Relation of antecedent illness to development of diabetes in children. Br Med J1980; 2: 99 – 101.CrossRefGoogle Scholar
  95. 95.
    Ratzman KP, Strese J, Witt S, Berling H, Keilacker H, Michaelis D. Mumps infection and insulin-dependent diabetes mellitus (IDDM). Diabetes Care1984; 7: 170 – 173.CrossRefGoogle Scholar
  96. 96.
    Oldstone MBA, Southern P, Rodriguez M, Lampert P. Virus persists in B cells of islets of Langerhans and is associated with chemical manifestations of diabetes. Science1984; 224: 1440 – 1443.PubMedCrossRefGoogle Scholar
  97. 97.
    Notkins AL, Yoon JW. Virus-induced diabetes, in Notkins AL, Oldstone MBA (eds): Concepts in Viral Pathogenesis. New York: Springer-Verlag, 1984; pp 241 – 247.Google Scholar
  98. 98.
    Gerling I, Nejman C, Chatterjee NK. Effect of Coxsackie B4 virus infection in mice on expression of 64,000-Mr autoantigen and glucose sensitivity of islets before development of hyperglycemia. Diabetes1988; 37: 1419 – 1425.PubMedCrossRefGoogle Scholar
  99. 99.
    Stefan Y, Malaisse-Lague F, Yoon JW, Notkins AL, Orci L. Virus-induced diabetes in mice: A quantitative evaluation of islet cell population by immunofluorescence technique. Diabetologia1978; 15: 395 – 401.PubMedCrossRefGoogle Scholar
  100. 100.
    Like AA, Rossini AA. Streptozotocin-induced pancreatic insulitis: New model of diabetes mellitus. Science1976; 193: 415 – 417.PubMedCrossRefGoogle Scholar
  101. 101.
    Like AA, Chick WL. Studies in the diabetic mutant mouse. II. Electron microscopy of pancreatic islets. Diabetologia1970; 6: 216 – 242.PubMedCrossRefGoogle Scholar
  102. 102.
    Leiter EH, Bedigian HG. Intracisternal type A particles in genetically diabetic mice: Identification in pancreas and induction in cultured B-cells. Diabetologia1979; 17: 175 – 185.PubMedCrossRefGoogle Scholar
  103. 103.
    Leiter EH, Kuff EL. Intracisternal type A particles in murine pancreatic B cells: Immunocytochemical demonstration of increased antigen (p73) in genetically diabetic mice. Am J Pathol1984; 114: 46 – 55.PubMedGoogle Scholar
  104. 104.
    Leiter EH, Fewell JW, Kuff EL. Glucose induces intracisternal type A retroviral gene transcription and translation in pancreatic B-cells. J Exp Med1986; 163: 87 – 100.PubMedCrossRefGoogle Scholar
  105. 105.
    Suenaga K, Yoon JW. Association of beta cell specific expression of endogenous retrovirus with the development of insulitis and diabetes NOD mouse. Diabetes1988; 37: 1722 – 1726.PubMedCrossRefGoogle Scholar

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  • Ji-Won Yoon

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