The role of interleukin-1 in the pathogenesis of IDDM

Diabetologia

Volumn 39, Issue 9, 1996, Pages 1005-1029

  Mandrup Poulsen, T ^a  

^a STENO DIABETES CENTER   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOKINE; INTERLEUKIN 1;

HUMAN; IMMUNE RESPONSE; IMMUNOGENETICS; INSULIN DEPENDENT DIABETES MELLITUS; MODEL; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; REVIEW;

EID: 0029817047     PISSN: 0012186X     EISSN: None     Source Type: Journal    
DOI: 10.1007/BF00400649     Document Type: Review

References (316)

1. Minkowski O (1929) Die Lehre vom Pankreas-Diabetes in ihrer geschichtlichen Entwicklung. Münchener Medizinische Wochenschrift 76: 311-315
2. Kroemer G, Martinez-A C (1992) Mechanisms of self tolerance. Immunol Today 13: 401-404
3. Dinarello CA (1994) The biological properties of interleukin-1. Eur Cytokine Netw 5: 517-531
4. Dustin ML, Springer TA (1991) Role of lymphocyte adhesion receptors in transient interactions and cell locomotion. Annu Rev Immunol 9: 27-66
5. Liu C-C, Walsh CM, Young JD-E (1995) Perform: structure and function. Immunol Today 16: 194-201
6. Smyth MJ, Trapani JA (1995) Granzymes: exogenous proteinases that induce target cell apoptosis. Immunol Today 16: 202-207
7. Irmler M, Hertig S, Robson Macdonald H, et al. (1995) Granzyme A is an interleukin 1β-converting enzyme. J Exp Med 181: 1917-1922
8. Doherty PC (1993) Cell-mediated cytotoxicity. Cell 75: 607-612
9. Romain PL, Schlossman SF (1984) Human T lymphocyte subsets. Functional heterogeneity and surface recognition structures. J Clin Invest 74: 1559-1565
10. Gumperz JE, Parham P (1995) The enigma of the natural killer cell. Nature 378: 245-248
11. Seljelid R (1987) Effector functions of macrophages. Acta Med Scand 715:[Suppl]131-138
12. + T cells in the pathogenesis of organ-specific autoimmune diseases. Immunol Today 16: 34-38
13. Cohen JJ, Duke RC, Fadok VA, Sellins KS (1992) Apoptosis and programmed cell death in immunity. Annu Rev Immunol 10: 267-293
14. Foulis AK, Liddle CN, Farquharson MA, Richmond JA, Weir RS (1986) The histopathology of the pancreas in type 1 (insulin-dependent) diabetes mellitus: a 25-year review of deaths in patients under 20 years of age in the United Kingdom. Diabetologia 29: 267-274
15. Foulis AK, McGill M, Farquharson MA (1991) Insulitis in type 1 (insulin-dependent) diabetes mellitus in man - macrophages, lymphocytes, and interferon-gamma containing cells. J Pathol 165: 97-103
16. Itoh N, Hanafusa T, Miyazaki A et al. (1993) Mononuclear cell infiltration and its relation to the expression of major histocompatibility complex antigens and adhesion molecules in pancreas biopsy specimens from newly diagnosed insulin-dependent diabetes mellitus patients. J Clin Invest 92: 2313-2322
17. Sibley RK, Sutherland DER, Goetz F, Michael AF (1985) Recurrent diabetes mellitus in the pancreas isoand allograft. A light and electron microscopic immunohistochemical analysis of four cases. Lab Invest 53: 132-144
18. Hanenberg H, Kolb-Bachofen V, Kantwerk-Funke G, Kolb H (1989) Macrophage infiltration precedes and is a prerequisite for lymphocytic insulitis in pancreatic islets of pre-diabetic BB rats. Diabetologia 32: 126-134
19. Vorbij HA, Jeucken PH, Kabel PJ, Haan MD, Drexhage HA (1989) Dendritic cells and scavenger macrophages in pancreatic islets of prediabetic BB rats. Diabetes 38: 1623-1629
20. Jansen A, Homo-Delarche F, Hooijkaas H, Leenen PJ, Dardenne M, Drexhage HA (1994) Immunohistochemical characterization of monocytes - macrophages and dendritic cells involved in the initiation of the insulitis and beta-cell destruction in NOD mice. Diabetes 43: 667-675
21. 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
22. Drell DW, Notkins AL (1987) Multiple immunological abnormalities in patients with type 1 (insulin-dependent) diabetes mellitus. Diabetologia 30: 132-143
23. Salvi M, Fukazawa H, Bernard N, Hiromatsu Y, How J, Wall JR (1988) Role of autoantibodies in the pathogenesis and association of endocrine autoimmune disorders. Endoer Rev 9: 450-466
24. Svenningsen A, Dyrberg T, Gerling I, Lernmark A, MacKay P, Rabinovitch A (1983) Inhibition of insulin release after passive transfer of immunoglobulin from insulin-dependent diabetic children to mice. J Clin Endocrinol Metab 57: 1301-1304
25. Tingle AJ, Lim G, Wright VJ, Dimmick JE, Hunt JA (1979) Transplacental passage of islet cell antibodies in infants of diabetic mothers. Pediatr Res 13: 1323-1325
26. Boitard C, Feutren G, Castano L et al. (1987) Effect of cyclosporin A treatment on the production of antibody in insulin-dependent (type 1) diabetic patients. J Clin Invest 80: 1607-1612
27. Mandrup-Poulsen T, Mølvig J, Andersen HU et al. (1990) Lack of predictive value of islet cell antibodies, insulin antibodies and HLA-DR phenotype for remission in cyclosporin-treated IDDM patients. Diabetes 39: 204-210
28. Petersen JS, Dyrberg T, Karlsen AE et al. (1994) Glutamic acid decarboxylase (GAD65) autoantibodies in prediction of β-cell function and remission in recent-onset IDDM after cyclosporin treatment. Diabetes 43: 1291-1296
29. Bendelac A, Boitard C, Bedossa P, Bazin H, Bach J-F, Carnaud C (1988) Adoptive T cell transfer of autoimmune nonobese diabetic mouse diabetes does not require recruitment of host B lymphocytes. J Immunol 141: 2625-2628
30. Vardi P, Dibella EE, Pasquarello TJ, Srikanta S (1987) Islet cell autoantibodies: pathobiology and clinical applications. Diabetes Care 10: 645-656
31. Weetman AP, McGregor AM (1994) Autoimmune thyroid disease: further developments in our understanding. Endocr Rev 15: 788-830
32. Via CS, Shearer GM (1988) T-cell interactions in autoimmunity: insights from a murine model of graft-versus-host disease. Immunol Today 9: 207-213
33. Ffrench-Constant C (1994) Pathogenesis of multiple sclerosis. Lancet 343: 271-275
34. + T cells in murine experimental allergic encephalomyelitis. Science 256: 1213-1215
35. Ellerman KE, Powers JM, Brostoff SW (1988) A suppressor T-lymphocyte cell line for autoimmune encephalomyelitis. Nature 331: 265-267
36. Charles MA, Suzuki M, Waldeck N et al. (1983) Immune islet killing mechanisms associated with insulin-dependent diabetes: in vitro expression of cellular and antibody-mediated islet cell cytotoxicity in humans. J Immunol 130: 1189-1194
37. Maruyama T, Takei I, Taniyama M, Kataoka K, Matsuki S (1984) Immunological aspect of non-obese diabetic mice: immune islet cell-killing mechanism and cell-mediated immunity. Diabetologia 27: 121-123
38. MacKay P, Boulton A, Rabinovitch A (1985) Lymphoid cells of BB/W diabetic rats are cytotoxic to islet beta cells in vitro. Diabetes 34: 706-709
39. Weringer EJ, Like AA (1985) Immune attack on pancreatic islet transplants in the spontaneously diabetic BioBreeding/Worcester (BB/W) rat is not MHC restricted. J Immunol 134: 2382-2386
40. Nomikos IN, Prowse SJ, Carotenuto P, Lafferty KJ (1986) Combined treatment with nicotinamide and desferrioxamine prevents islet allograft destruction in NOD mice. Diabetes 35: 1302-1304
41. Katz J, Benoist C, Mathis D (1993) Major histocompatibility complex class I molecules are required for the development of insulitis in non-obese diabetic mice. Eur J Immunol 23: 3358-3360
42. + -T-lymphocytes grown from islets of NOD mice. Diabetes Res 16: 69-73
43. + T-cells are required for adoptive transfer of the BB rat diabetic syndrome. Diabetes 42: 390-397
44. + T-cell clones derived from lymphocytes infiltrating the islets of NOD mice. Diabetes 41: 998-1007
45. + T cell subsets are required for the transfer of diabetes in nonobese diabetic mice. J Immunol 140: 52-58
46. + islet-specific T-cell clone. Diabetes 41: 1603-1608
47. + T cells in autoimmune diabetes of NOD mice using transfer to NOD athymic nude mice. Eur J Immunol 22: 2387-2393
48. + T cells from diabetic versus prediabetic NOD.NON-thy-1a donors. Diabetes 42: 44-55
49. Katz JD, Benoist C, Mathis D (1995) T helper cell subsets in insulin-dependent diabetes. Science 268: 1185-1188
50. + memory T cells secrete T-helper type 1 and type 2 cytokines and provide help for immunoglobin secretion. Eur J Immunol 24: 3087-3092
51. + T helper type 2 cells. J Exp Med 181: 5-7
52. Lipes MA, Rosenzweig A, Tan K-N et al. (1993) Progression to diabetes in nonobese diabetic (NOD) mice with transgenic T cell receptors. Science 259: 1165-1169
53. Kolb-Bachofen V, Kolb H (1989) A role for macrophages in the pathogenesis of type 1 diabetes. Autoimmunity 3: 145-155
54. Schwitzer RW, Leiter EH, Evans R (1984) Macrophage-mediated cytotoxicity against cultured pancreatic islet cells. Transplantation 37: 539-544
55. Appels B, Burkart V, Kantwerk-Funke G, Funda J, Kolb-Bachofen V, Kolb H (1989) Spontaneous cytotoxicity of macrophages against pancreatic islet cells. J Immunol 142: 3803-3808
56. Varsanyi Nagy M, Chan EK, Teruya M, Forrest LE, Likhite V, Charles MA (1989) Macrophage-mediated islet cell cytotoxicity in BB rats. Diabetes 38: 329-1331
57. Davies AJ, Bone AJ, Wilkin TJ, Rokos H, Cole DR (1994) Serum biopterin - a novel marker for immune activation during pre-diabetes in the BB rat. Diabetologia 37: 466-470
58. Brenner HH, Burkart V, Rothe H, Kolb H (1993) Oxygen radical production is increased in macrophages from diabetes prone BB rats. Autoimmunity 15: 93-98
59. Shimada A, Takei I, Maruyama T et al. (1994) Acceleration of diabetes in young NOD mice with peritoneal macrophages. Diabetes Res Clin Pract 24: 69-76
60. Oschilewski U, Kiesel U, Kolb H (1985) Administration of silica prevents diabetes in BB-rats. Diabetes 34: 197-199
61. Amano K, Yoon J-W (1990) Studies on autoimmunity for initiation of β-cell destruction. V. Decrease of macrophage-dependent T-lymphocytes and natural killer cytotoxicity in silica-treated BB-rats. Diabetes 39: 590-596
62. Hutchings P, Rosen H, O'Reilly L, Simpson E, Gordon S, Cooke A (1990) Transfer of diabetes in mice prevented by blockade of adhesion-promoting receptor on macrophages. Nature 348: 639-642
63. Kröncke K, Kolb-Bachofen V, Berschick B, Burkart V, Kolb H (1991) Activated macrophages kill pancreatic syngeneic islet cells via arginine-dependent nitric oxide generation. Biochem Biophys Res Commun 175: 752-758
64. Kröncke K, Funda J, Berschick B, Kolb H, Kolb-Bachofen V (1991) Macrophage cytotoxicity towards isolated rat islet cells: neither lysis nor its protection by nicotinamide are beta-cell specific. Diabetologia 34: 232-238
65. Ihm S-H, Yoon J-W (1990) Studies on autoimmunity for initiation of β-cell destruction. VI. Macrophages essential for development of β-cell specific cytotoxic effectors and insulitis in NOD mice. Diabetes 39: 1273-1278
66. Krall G, Martens G, Kuystermans K (1993) Systemic elimination of macrophages using liposomes does not prevent the induction of type I diabetes. Int Arch Allergy Immunol 100: 115-120
67. Serreze DV, Gaedeke JW, Leiter HH (1993) Hematopoietic stem-cell defects underlying abnormal macrophage development and maturation in NOD/Lt mice: defective regulation of cytokine receptors and protein kinase C. Proc Natl Acad Sci 90: 9625-9629
68. Tafuri A, Bowers WE, Handler ES et al. (1993) High stimulatory activity of dendritic cells from diabetes-prone BioBreeding/Worcester rats exposed to macrophage-derived factors. J Clin Invest 91: 2040-2048
69. Woda BA, Biron CA (1986) Natural killer cell number and function in the spontaneously diabetic BB/W rat. J Immunol 137: 1860-1866
70. MacKay P, Jacobsen J, Rabinovitch A (1986) Spontaneous diabetes mellitus in the Bio-breeding/Worcester rat. Evidence in vitro for natural killer cell lysis of islet cells. J Clin Invest 77: 916-924
71. Like AA, Biron CA, Weringer EJ, Byman K, Sroczynski E, Guberski DL (1986) Prevention of diabetes in BioBreeding/Worcester rats with monoclonal antibodies that recognize T lymphocytes or natural killer cells. J Exp Med 164: 1145-1159
72. Ellerman K, Wrobleski M, Rabinovitch A, Like AA (1993) Natural killer cell depletion and diabetes mellitus in the BB/Wor rat (revisited). Diabetologia 36: 596-601
73. Lernmark A, Kloppel G, Stenger D et al. (1995) Heterogeneity of islet pathology in two infants with recent onset diabetes mellitus. Virchows Arch 425: 631-640
74. Mandrup-Poulsen T, Bendtzen K, Nielsen JH, Bendixen G, Nerup J (1985) Cytokines cause functional and structural damage to isolated islets of Langerhans. Allergy 40: 424-429
75. Mandrup-Poulsen T, Bendtzen K, Nerup J, Egeberg J, Nielsen JH (1986) Mechanisms of pancreatic islet cell destruction. Dose-dependent cytotoxic effect of soluble blood mononuclear cell mediators on isolated islets of Langerhans. Allergy 41: 250-259
76. Mandrup-Poulsen T, Bendtzen K, Nerup J, Dinarello CA, Svenson M, Nielsen JH (1986) Affinity-purified human interleukin 1 is cytotoxic to isolated islets of Langerhans. Diabetologia 29: 63-67
77. Bendtzen K, Mandrup-Poulsen T, Nerup J, Nielsen JH, Dinarello CA, Svenson M (1986) Cytotoxicity of human pl 7 interleukin-1 for pancreatic islets of Langerhans. Science 232: 1545-1547
78. Mandrup-Poulsen T, Egeberg J, Nerup J, Bendtzen K, Nielsen JH, Dinarello CA (1987) Ultrastructural study of time-course and cellular specificity of interleukin-1 mediated islet cytotoxicity. APMIS 95: 55-63
79. Sandler S, Bendtzen K, Borg LAH, Eizirik DL, Strandell E, Welsh N (1989) Studies on the mechanisms causing inhibition of insulin secretion in rat pancreatic islets exposed to human interleukin-β indicate a perturbation in the mitochondrial function. Endocrinology 124: 1492-1501
80. Helqvist S, Zumsteg UW, Spinas GA et al. (1991) Repetitive exposure of pancreatic islets to interleukin-β. An in vitro model of pre-diabetes? Autoimmunity 10: 311-318
81. Sandler S, Andersson A, Hellerström C (1987) Inhibitory effects of interleukin 1 on insulin secretion, insulin biosynthesis, and oxidative metabolism of isolated rat pancreatic islets. Endocrinology 121: 1424-1431
82. Delaney CA, Green MHL, Lowe JE, Green IC (1993) Endogenous nitric oxide induced by interleukin-β in rat islets of Langerhans and HIT-T15 cells causes significant DNA damage as measured by the "cometi" assay. FEBS Lett 333: 291-295
83. Bolaffi JL, Rodd GG, Wang J, Grodsky GM (1994) Interrelationship of changes in islet nicotine adeninedinucleotide, insulin secretion, and cell viability induced by interleukin-β. Endocrinology 134:537-542
84. Sandler S, Bendtzen K, Eizirik DL, Sjöholm Å, Welsh N (1989) Decreased cell replication and polyamine content in insulin-producing cells after exposure to human interleukin 1β. Immunol Lett 22: 267-272
85. Janjic D, Asfari M (1992) Effects of cytokines on rat insulinoma INS-1 cells. J Endocrinol 132: 67-76
86. Hamaguchi K, Leiter EH (1990) Comparison of cytokine effects on mouse pancreatic α-cell and β-cell lines. Viability, secretory function and MHC antigen expression. Diabetes 39: 415-125
87. Wogensen LD, Kolb-Bachofen V, Christensen P et al. (1990) Functional and morphological effects of interleukin-β on the perfused rat pancreas. Diabetologia 33: 15-23
88. Mandrup-Poulsen T, Bendtzen K, Dinarello CA, Nerup J (1987) Human tumor necrosis factor potentiates human interleukin 1-mediated rat pancreatic β-cell cytotoxicity. J Immunol 139: 4077-4082
89. Eizirik DL (1988) Interleukin-1 induced impairment in pancreatic islet oxidative metabolism of glucose is potentiated by tumor necrosis factor. Acta Endocrinol 119: 321-325
90. Sandler S, Sternesjö J (1995) Interleukin 4 impairs rat pancreatic islet function in vitro by an action different to that of interleukin 1. Cytokine 7: 296-300
91. Corbett JA, McDaniel ML (1995) Intraislet release of interleukin 1 inhibits β cell function by inducing β cell expression of inducible nitric oxide synthase. J Exp Med 181: 559-568
92. Nielsen JH, Mandrup-Poulsen T, Spinas GA et al. (1986) Possible role of interleukin.1 (IL-1) in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). In: Jaworsky M (ed) The immunology of diabetes mellitus. Excerpta Medica Int Congr Ser 717, Amsterdam, pp 97-103
93. Rabinovitch A, Pukel C, Baquerizo H (1988) Interleukin-1 inhibits glucose-modulated insulin and glucagon secretion in rat islet monolayer cultures. Endocrinology 122: 2393-2398
94. Corbett JA, Wang JL, Sweetland MA, Lancaster JR Jr, McDaniel ML (1992) Interleukin 1β induces the formation of nitric oxide by β-cells purified from rodent islets of Langerhans. Evidence for the β cell as a source and site of action of nitric oxide. J Clin Invest 90: 2384-2391
95. Zhidong L, In't Veld PA, Pipeleers DG (1993) Interaction of interleukin-1 with islet β-cells. Distinction between indirect, aspecific cytotoxicity and direct, specific functional suppression. Diabetes 42: 56-65
96. Pukel C, Baquerizo H, Rabinovitch A (1988) Destruction of rat islet cell monolayers by cytokines. Synergistic interactions of interferon-gamma, tumor necrosis factor, lymphotoxin and interleukin 1. Diabetes 37: 133-136
97. Rabinovitch A, Baquerizo H, Pukel C, Sumoski W (1989) Effects of cytokines on rat pancreatic islet cell monolayer cultures: distinction between functional and cytotoxic effects on islet β-cells. Reg Immunol 2: 77-82
98. Eizirik DL, Welsh M, Strandell E, Welsh N, Sandler S (1990) Interleukin-β depletes insulin messenger ribonucleic acid and increases the heat shock protein hsp70 in mouse pancreatic islets without impairing the glucose metabolism. Endocrinology 127: 2290-2297
99. Eizirik DL (1991) Interleukin-1β induces an early decrease in insulin release, (pro)insulin biosynthesis and insulin mRNA in mouse pancreatic islets by a mechanism dependent on gene transcription and protein synthesis. Autoimmunity 10: 107-113
100. Welsh N, Sandler S (1992) Interleukin-1β induces nitric oxide production and inhibits the activity of aconitase without decreasing glucose oxidation rates in isolated mouse pancreatic islets. Biochem Biophys Res Commun 182: 333-340
101. Campbell IL, Ischaro A, Harrison LC (1988) IFN-gamma and tumor necrosis factor-α. Cytotoxicity to murine islets of Langerhans. J Immunol 141: 2325-2329
102. Kawahara DJ, Everts M, Sandborg C, Berman M, Buckingham B (1988) Cytokine-mediated killing of bovine islets is prevented by an interleukin-1 inhibitor. Diabetes 37:[Suppl 1]19A (Abstract)
103. Arias J, Vara E, Gómez M, Garcia C, Moreno A, Balibrea JL (1992) Effect of cytokines on "de novoi" lipid synthesis and hormone secretion by isolated human islets. Transplant Proc 24: 2909-2912
104. Zumsteg UW, Reimers JI, Pociot F et al. (1993) Differential interleukin-1 receptor antagonism on pancreatic beta and alpha cells. Studies in rodent and human islets and in normal rats. Diabetologia 36: 759-766
105. Mandrup-Poulsen T (1988) On the pathogenesis of insulin-dependent diabetes mellitus. Dan Med Bull 35: 438-460
106. Kawahara DJ, Kenney JS (1991) Species differences in human and rat islet sensitivity to human cytokines. Monoclonal anti-interleukin-1 (IL-1) influences on direct and indirect IL-1-mediated islet effects. Cytokine 3: 117-124
107. Eizirik DL, Welsh N, Hellerström C (1993) Predominance of stimulatory effects of interleukin-β on isolated human pancreatic islets. J Clin Endocrinol Metab 76: 399-403
108. Soldevila G, Buscema M, Doshi M, James RFL, Bottazzo GF, Pujol-Borrel R (1991) Cytotoxic effects of IFN-gamma plus TNFα on human islet cells. J Autoimmun 4: 291-306
109. Rabinovitch A, Sumoski W, Rajotte RV, Warnock GL (1990) Cytotoxic effects of cytokines on human pancreatic islet cells in monolayer culture. J Clin Endocrinol Metab 71: 152-156
110. Rabinovitch A, Suarez-Pinzon WL, Strynadka K et al. (1994) Human pancreatic islet β-cell destruction by cytokines is independent of nitric oxide production. J Clin Endocrinol Metab 79: 1058-1062
111. Eizirik DL, Pipeleers DG, Ling Z, Welsh N, Hellerström C, Andersson A (1994) Major species differences between humans and rodents in the susceptibility to pancreatic β-cell injury. Proc Natl Acad Sci 91: 9253-9256
112. Welsh N, Margulis B, Borg LAH et al. (1995) Differences in the expression of heat-shock proteins and antioxidant enzymes between human and rodent pancreatic islets: implications for the pathogenesis of insulin-dependent diabetes mellitus. Molecular Medicine 1: 806-820
113. Margulis B, Sandler S, Eizirik DL, Welsh N, Welsh M (1991) Liposomal delivery of purified heat shock protein hsp70 into rat pancreatic islets as protection against interleukin 1β-induced impaired β-cell function. Diabetes 40: 1418-1421
114. Reimers JI, Andersen HU, Mauricio D et al. (1996) Strain-dependent differences in sensitivity of rat beta-cells to IL-1β in vitro and in vivo: association with islet nitric oxide synthesis. Diabetes 45: 771-778
115. Held W, MacDonald HR, Weissman IL, Hess MW, Mueller C (1990) Genes encoding tumor necrosis factor a and granzyme A are expressed during development of autoimmune diabetes. Proc Natl Acad Sci 87: 2239-2243
116. Jiang Z, Woda BA (1991) Cytokine gene expression in the islets of the diabetic BioBreeding/Worcester rat. J Immunol 146: 2990-2994
117. Zunino SJ, Jiang N, Sambrook JF, Gething MJH (1992) Interleukin-1 α expression in islets of NOD mice. FASEB J 6:A1780 (Abstract)
118. Toyoda H, Formby B, Magalong D et al. (1994) In situ islet cytokine gene expression during development of type I diabetes in the non-obese diabetic mouse. Immunol Lett 39: 283-288
119. Huang X, Hultgren B, Dybdal N, Stewart TA (1994) Islet expression of interferon-α precedes diabetes in both the BB rat and streptozotocin-treated mice. Immunity 1: 469-478
120. Rabinovitch A, Suarez-Pinzon WL, Sorensen O, Bleackley RC, Power RF (1995) INF-gamma gene expression in pancreatic islet-infiltrating mononuclear cells correlates with autoimmune diabetes in NOD mice. J Immunol 154: 4874-4882
121. Rothe H, Burkart V, Faust A, Kolb H (1996) Interleukin-12 gene expression is associated with rapid development of diabetes mellitus in non-obese diabetic mice. Diabetologia 39: 119-122
122. Campbell IL, Kay TWH, Oxbrow L, Harrison LC (1991) Essential role for interferon-gamma and interleukin-6 in autoimmune insulin-dependent diabetes in NOD/Wehi mice. J Clin Invest 87: 739-742
123. Welsh M, Welsh N, Bendtzen K et al. (1995) Comparison of mRNA contents of interleukin-β and nitric oxide synthase in pancreatic islets isolated from female and male nonobese diabetic mice. Diabetologia 38: 153-160
124. Chosich N, Rockett E, Harrison LC (1994) Endogenous TNF production differs between high and low diabetes incidence non-obese diabetic (NOD) mice. Autoimmunity 18: 163-168
125. Rothe H, Fehsel K, Kolb H (1990) Tumor necrosis factor alpha production is upregulated in diabetes prone BB rats. Diabetologia 33: 573-575
126. Lapchak PH, Guilbert LJ, Rabinovitch A (1992) Tumor necrosis factor production is deficient in diabetes-prone BB rats and can be corrected by complete Freund's adjuvant: a possible immunoregulatory role of tumor necrosis factor in the prevention of diabetes. Clin Immunol Immunopathol 65: 129-134
127. Setoguchi J, Hashiramoto K et al. (1992) Prediction of insulin dependent diabetes mellitus in non-obese diabetic mice by the endogeneous tumor necrosis factor-alpha level. Diabetes Res 19: 63-67
128. Wogensen LD, Reimers JI, Nerup J et al. (1992) Repetitive in vivo treatment with human recombinant interleukin-β modifies beta-cell function in normal rats. Diabetologia 35: 331-339
129. Reimers JI, Bjerre U, Mandrup-Poulsen T, Nerup J (1994) Interleukin 1β induces diabetes and fever in normal rats by nitric oxide via induction of different nitric oxide synthases. Cytokine 6: 512-520
130. Shimizu H, Tanaka S, Mori M (1992) Adrenalectomy enhances the susceptibility of pancreatic islets to interleukin-1β: immunohistochemical study. Endocrinol Japon 39: 485-490
131. Wang Y, Goodman M, Lumerman J et al. (1989) In vivo administration of interleukin-1 inhibits glucose-stimulated insulin release. Diabetes Res Clin Pract 7: 205-211
132. Sutton R, Gray DWR, McShane P, Dallman MJ, Morris PJ (1989) The specificity of rejection and the absence of susceptibility of pancreatic islet β cells to nonspecific immune destruction in mixed strain islets grafted beneath the renal capsule in the rat. J Exp Med 170: 751-762
133. Korsgren O, Jansson L (1994) Characterization of mixed syngeneic-allogeneic and syngeneic-xenogeneic islet-graft rejections in mice. J Gin Invest 93: 1113-1119
134. + T cell-depleted mice. Transplantation 49: 849-856
135. + T lymphocytes in primary nonfunction and classic rejection of islet allografts. J Exp Med 172: 291-302
136. Dallman MJ, Porter ACG, Larsen CP, Morris PJ (1989) Lymphokine production in allografts - analysis of RNA by Northern blotting. Transplant Proc 21: 296-298
137. O'Connell PJ, Pacheco-Silva A, Nickerson PW et al. (1993) Unmodified pancreatic islet allograft rejection results in the preferential expression of certain T cell activation transcripts. J Immunol 150: 1093-1104
138. Sandberg J-O, Eizirik DL, Sandler S, Tracey DE, Andersson A (1993) Treatment with an interleukin-1 receptor antagonist protein prolongs mouse islet allograft survival. Diabetes 42: 1845-1851
139. Taverne J (1993) Transgenic mice in the study of cytokine function. Int J Exp Pathol 74: 525-546
140. Stewart TA, Hultgren B, Huang X, Pitts-Meek S, Hully J, MacLachlan NJ (1993) Induction of type 1 diabetes by interferon-α in transgenic mice. Science 260: 1942-1946
141. Sarvetnick N, Liggitt D, Pitts SL, Hansen SE, Stewart TA (1988) Insulin-dependent diabetes mellitus induced in transgenic mice by ectopic expression of class II MHC and interferon-gamma. Cell 52: 773-782
142. Allison J, Malcolm L, Chosich N, Miller JF (1992) Inflammation but not autoimmunity occurs in transgenic mice expressing constitutive levels of interleukin-2 in islet beta cells. Eur J Immunol 22: 1115-1121
143. DiCosmo BF, Picarella D, Flavell RA (1994) Local production of human IL-6 promotes insulitis but retards the onset of insulin-dependent diabetes mellitus in non-obese diabetic mice. Int Immunol 6: 1829-1837
144. Higuchi Y, Herrera P, Muniesa P et al. (1992) Expression of a tumor necrosis factor α transgene in murine pancreatic β cells results in severe and permanent insulitis without evolution towards diabetes. J Exp Med 176: 1719-1731
145. Picarella DE, Kratz A, Chang-ben L, Ruddle NH, Flavell RA (1992) Insulitis in transgenic mice expressing tumor necrosis factor β (lymphotoxin) in the pancreas. Proc Natl Acad Sci 89: 10036-10040
146. Wogensen LD, Huang X, Sarvetnick N (1993) Leukocyte extravasation into the pancreatic tissue in transgenic mice expressing interleukin 10 in the islets of Langerhans. J Exp Med 178: 175-185
147. Allison J, McClive P, Oxbrow L, Baxter A, Morahan G, Miller JFAP (1994) Genetic requirements for acceleration of diabetes in non-obese diabetic mice expressing interleukin-2 in islet β-cells. Eur J Immunol 24: 2535-2541
148. Wogensen LD, Myung-Shik L, Sarvctnick N (1994) Production of interleukin 10 by islet cells accelerates immune-mediated destruction of β cells in nonobese diabetic mice. J Exp Med 179: 1379-1384
149. Moritani M, Yoshimoto K, Tashiro F et al. (1994) Transgenic expression of IL-10 in pancreatic islet A cells accelerates autoimmune insulitis and diabetes in non-obese diabetic mice. Int Immunol 6: 1927-1936
150. Myung-Shik L, Wogensen LD, Shizuru J, Oldstone MBA, Sarvetnick N (1994) Pancreatic islet production of murine interleukin-10 does not inhibit immune-mediated tissue destruction. J Clin Invest 93: 1332-1338
151. Guerder S, Picarella D, Linsley PS, Flavell RA (1994) Co-stimulator B7-1 confers antigen-presenting-cell function to parenchymal tissue and in conjunction with tumor necrosis factor alpha leads to autoimmunity in transgenic mice. Proc Natl Acad Sci 91: 5138-5142
152. Wilson CA, Jacobs C, Baker P, Baskin DG, Dower S, Lernmark A et al. (1990) IL-1β modulation of spontaneous autoimmune diabetes and thyroiditis in the BB rat. J Immunol 144: 3784-3788
153. Vertrees S, Wilson CA, Ubungen R et al. (1991) Interleukin-1β regulation of islet and thyroid autoimmunity in the BB rat. J Autoimmun 4: 717-732
154. Jacob CO, Aiso S, Michie SA, McDevitt HO, Acha-Orbea H (1990) Prevention of diabetes in nonobese diabetic mice by tumor necrosis factor (TNF): similarities between TNF-α and interleukin-1. Proc Natl Acad Sci 87: 968-972
155. Reimers JI, Mørch L, Markholst H et al. (1994) Interleukin-1β (IL-1) does not reduce the diabetes incidence in diabetes-prone BB rats. Autoimmunity 17: 105-118
156. Formby B, Jacobs C, Dubuc P, Shao T (1992) Exogenous administration of IL-α inhibits active and adoptive transfer autoimmune diabetes in NOD mice. Autoimmunity 12: 21-27
157. Kolb H, Zielasek J, Treichel U, Freytag G, Wrann M, Kiesel U (1986) Recombinant interleukin 2 enhances spontaneous insulin-dependent diabetes in BB rats. Eur J Immunol 16: 209-212
158. Burstein D, Handler ES, Schindler J, Seals J, Mordes JP, Rossini AA (1987) Effect of interleukin-2 on diabetes in the BB/Wor rat. Diabetes Res 5: 163-167
159. Serreze DV, Hamaguchi K, Leiter EH (1989) Immunostimulation circumvents diabetes in NOD/Lt mice. J Autoimmun 2: 759-776
160. Satoh J, Seino H, Shintani S, et al. (1990) Inhibition of type 1 diabetes in BB rats with recombinant human tumor necrosis factor-α. J Immunol 145: 1395-1399
161. Yang X-D, Tisch R, Singer SM et al. (1994) Effect of tumor necrosis factor α on insulin-dependent diabetes mellitus in NOD mice. I. The early development of autoimmunity and the diabetogenic process. J Exp Med 180: 995-1004
162. Satoh J, Seino H, Abo R et al. (1989) Recombinant tumor necrosis factor α suppresses autoimmune diabetes in nonobese diabetic mice. J Clin Invest 84: 1345-1348
163. Zunino S, Simons L, Sambrook JF, Gething MJH (1994) Interleukin-1 promotes hyperglycemia and insulitis in mice normally resistant to streptozotocin-induced diabetes. Am J Pathol 145: 661-670
164. Takahashi K, Satoh J, Seino H et al. (1993) Prevention of type I diabetes with lymphotoxin in BB rats. Clin Immunol Immunopathol 69: 318-323
165. Seino H, Takahashi K, Satoh J et al. (1993) Prevention of autoimmune diabetes with lymphotoxin in NOD mice. Diabetes 42: 398-404
166. Trembleau S, Penna G, Bosi E, Mortara A, Gately MK, Adorini L (1995) Interleukin 12 administration induces T helper type 1 cells and accelerates autoimmune diabetes in NOD mice. J Exp Med 181: 817-821
167. Rapoport MJ, Jaramillo A, Zipris D et al. (1993) Interleukin 4 reverses T cell proliferative unresponsiveness and prevents the onset of diabetes in nonobese diabetic mice. J Exp Med 178: 87-99
168. Pennline KJ, Roque-Gaffney E, Monahan M (1994) Recombinant human IL-10 prevents the onset of diabetes in the nonobese diabetic mouse. Clin Immunol Immunopathol 71: 169-175
169. Watanabe Y, Inoue I, Inaba T et al. (1993) Effect of macrophage colony-stimulating factor on the development of diabetes mellitus in BB rats. Horm Metab Res 25: 323-324
170. Campbell IL, Oxbrow L, Harrison LC (1991) Reduction in insulitis following administration of IFN-gamma and TNF-α in the NOD mouse. J Autoimmun 4: 249-262
171. Sobel DO, Newsome J, Ewel CH et al. (1992) Poly I:C induces development of diabetes mellitus in BB rat. Diabetes 41: 515-520
172. Dayer-Métroz M-D, Duhamel D, Rufer N et al. (1992) IL-1 receptor antagonist delays spontaneous autoimmune diabetes in BB rats. Eur J Clin Invest 22:A50 (Abstract)
173. Lukic M, Stosic S (1993) Interleukin I receptor antagonists prevent the induction of autoimmune diabetes. Autoimmunity 14:[Suppl 1]12
174. Nicoletti F, Di Marco R, Barcellini W et al. (1994) Protection from experimental autoimmune diabetes in the nonobese diabetic mouse with soluble interleukin-1 receptor. Eur J Immunol 24: 1843-1847
175. Jacob CO, Aiso S, Schreiber RD, McDevitt HO (1992) Monoclonal anti-tumor necrosis factor antibody renders non-obese diabetic mice hypersensitive to
176. Nicoletti F, Meroni P, Landolfo S et al. (1990) Prevention of diabetes in BB/Wor rats treated with monoclonal antibodies to interferon-gamma. Lancet 336: 319
177. Debray-Sachs M, Carnaud C, Boitard C et al. (1991) Prevention of diabetes in NOD mice treated with antibody to murine IFN-gamma. J Autoimmun 4: 237-248
178. Serreze DV, Leiter EH (1988) Defective activation of T suppressor cell function in nonobese diabetic mice: potential relation to cytokine deficiencies. J Immunol 140: 3801-3807
179. Tilg H, Atkins MB, Dinarello CA, Mier JW (1995) Induction of circulating interleukin 10 by interleukin 1 and interleukin 2, but not interleukin 6 immunotherapy. Cytokine 7: 734-739
180. Foulis AK, Farquharson MA, Meager A (1987) Immunoreactive α-interferon in insulin-secreting beta cells in type 1 diabetes mellitus. Lancet ii:1423-1427
181. Somoza N, Vargas F, Roura-Mir C et al. (1994) Pancreas in recent onset insulin-dependent diabetes mellitus. Changes in HLA, adhesion molecules and autoantigens, restricted T cell receptor Vβ usage, and cytokine profile. J Immunol 153: 1360-1377
182. Hussain MJ, Peakman M, Gallati H et al. (1996) Elevated serum levels of macrophage-derived cytokines precede and accompany the onset of IDDM. Diabetologia 39: 60-69
183. Cavallo MG, Pozzilli P, Bird C et al. (1991) Cytokines in sera from insulin-dependent diabetic patients at diagnosis. Clin Exp Immunol 86: 256-259
184. Lorini R, De Amici M, d'Annunzio G, Vitali L, Scaramuzza A (1995) Low serum levels of tumor necrosis factor-alpha in insulin-dependent diabetic children. Horm Res 43: 206-209
185. Ciampolillo A, Guastamacchia E, Caragiulo L et al. (1993) In vitro secretion of interleukin-1β and interferon-gamma by peripheral blood lymphomononuclear cells in diabetic patients. Diabetes Res Clin Pract 21: 87-93
186. Sahdev I, Fort P, Herry A (1992) Macrophage-released interleukin-1 in patients with type 1 diabetes mellitus. Acta Paediatr Scand 81: 935-936
187. Giordano C, Panto F, Caruso C et al. (1989) Interleukin 2 and soluble interleukin 2-receptor secretion defect in vitro in newly diagnosed type 1 diabetic patients. Diabetes 38: 310-315
188. Luger A, Schernthaner G, Urbanski A, Luger TA (1988) Cytokine production in patients with newly diagnosed insulin-dependent (type 1) diabetes mellitus. Eur J Clin Invest 18: 233-236
189. Mølvig J, Pociot F, Baek L, et al. (1990) Monocyte function in IDDM patients and healthy individuals. Scand J Immunol 32: 297-311
190. Zier KS, Spielman RS, Baker L (1984) Decreased synthesis of interleukin-2 (IL-2) in insulin-dependent diabetes mellitus. Diabetes 33: 552-555
191. Lang F, Pogu S, Maurel C, Charbonnel B, Sai P (1987) Production of and response to interleukin 2 by blood mononuclear cells from some type 1 diabetic patients. Diabete Metabol 13: 37-43
192. Ohno Y, Aoki N, Nishimura A (1993) In vitro production of interleukin-1, interleukin-6 and tumor necrosis factor-α in insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 77: 1072-1077
193. Tomoda T, Kurashige T, Taniguchi T (1994) Imbalance of the interleukin 2 system in children with IDDM. Diabetologia 37: 476-482
194. Ilonen J, Salonen R, Mustonen A (1989) Low levels of mumps virus antigen induced interferon-alpha production in insulin-dependent diabetes. Diabetes Res 12: 75-78
195. Sachs JA, Whichelow CE, Hitman GA, Niven M, Thode H, Meager A (1990) The effect of HLA and insulin-dependent diabetes mellitus on the secretion levels of tumour necrosis factor alpha and beta and gamma interferon. Scand J Immunol 32: 703-708
196. Imagawa A, Itoh N, Hanafusa T, Waguri M, Kuwajima M, Matsuzawa Y (1996) Antibodies to glutamic acid decarboxylase induced by interferon-alpha therapy for chronic viral hepatitis. Diabetologia 39: 126
197. Waguri M, Hanafusa T, Itoh N et al. (1994) Occurrence of IDDM during interferon therapy for chronic viral hepatitis. Diabetes Res Clin Pract 23: 33-36
198. Kyvik K, Green A, Beck-Nielsen H (1995) Concordance rates of insulin dependent diabetes mellitus: a population based study of young Danish twins. BMJ 311: 913-917
199. Thomson G, Robinson WP, Kuhner MK et al. (1988) Genetic heterogeneity, modes of inheritance, and risk estimates for a joint study of Caucasians with insulin-dependent diabetes mellitus. Am J Hum Genet 43: 799-816
200. Davies JL, Kawaguchi Y, Bennett ST et al. (1994) A genome-wide search for human type 1 diabetes susceptibility genes. Nature 371: 130-136
201. Copeman JB, Cucca F, Hearne CM et al. (1995) Linkage disequilibrium mapping of a type 1 diabetes susceptibility gene (IDDM7) to chromosome 2q31-q33. Nature Genet 9: 80-85
202. Cornall RJ, Prins J-B, Todd JA et al. (1991) Type 1 diabetes in mice is linked to the interleukin-1 receptor and Lsh/Ity/Bcg genes on chromosome 1. Nature 353: 262-265
203. Pociot F, Mølvig J, Wogensen LD, Worsaae H, Nerup J (1992) A Taql polymorphism in the human interleukin-1β (IL-1β) gene correlates with IL-1β secretion in vitro. Eur J Clin Invest 22: 396-402
204. Pociot F, Rønningen KS, Bergholdt R et al. (1994) Genetic susceptibility markers in Danish patients with type 1 (insulin-dependent) diabetes - evidence for polygenecity in man. Autoimmunity 19: 169-178
205. Mandrup-Poulsen T, Pociot F, Mølvig J et al. (1994) Monokine antagonism is reduced in patients with IDDM. Diabetes 43: 1242-1247
206. Bergholdt R, Karlsen AE, Johannesen J et al. (1995) Characterization of polymorphisms of an interleukin 1 receptor type 1 gene (IL1R1) promotor region (P2) and their relation to insulin-dependent diabetes mellitus (IDDM). Cytokine 7: 727-733
207. Metcalfe KA, Hitman GA, Pociot F et al. (1995) A transracial study of association between IDDM and the interleukin-1 receptor type 1 gene. Diabetologia 38:[Suppl 1]A72 (Abstract)
208. Pociot F, Briant L, Jongeneel CV et al. (1993) Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF-α and TNF-β by human mononuclear cells: a possible link to insulin-dependent diabetes mellitus. Eur J Immunol 23: 224-231
209. Awata T, Matsumoto C, Urakami T, Hagura R, Amemiya S, Kanazawa Y (1994) Association of polymorphism in the interferon gamma gene with IDDM. Diabetologia 37: 1159-1162
210. Johannesen J, Vejijola R, Hansen PM et al. (1995) Analysis of polymorphism in the interferon-gamma gene in Danish and Finnish IDDM patients and control subjects. Diabetologia 38:[Suppl 1]A29 (Abstract)
211. Sandler S, Eizrik DL, Svensson C, Strandell E, Welsh M, Welsh N (1991) Biochemical and molecular actions of interleukin-1 on pancreatic β-cells. Autoimmunity 10: 241-253
212. Corbett JA, McDaniel ML (1992) Does nitric oxide mediate autoimmune destruction of β-cells? Diabetes 41: 897-903
213. Dinarello CA (1994) The interleukin-1 family: 10 years of discovery. FASEB J 8: 1314-1325
214. Greenfelder SA, Nunes P, Kwee L, Labow M, Chizzonite RA (1995) Molecular cloning and characterization of a second subunit of the interleukin 1 receptor complex. J Biol Chem 270: 13757-13765
215. Brooks JW, Mizel SB (1994) Interleukin-1 signal transduction. Eur Cytokine Netw 5: 547-561
216. Hammonds P, Beggs M, Beresford G, Espinal J, Clarke J, Mertz RJ (1990) Insulin-secreting β-cells possess specific receptors for interleukin-1β. FEBS Lett 261: 97-100
217. Deyerle KL, Sims JE, Dower SK, Bothwell MA (1992) Pattern of IL-1 receptor gene expression suggests role in noninflammatory processes. J Immunol 149: 1657-1665
218. Eizirik DL, Björklund A, Welsh N (1993) Interleukin-1 induced expression of nitric oxide synthase in insulin-producing cells is preceded by c-fos induction and depends on gene transcription and protein synthesis. FEBS Lett 317: 62-66
219. Jafarian-Tehrani M, Amrani A, Homo-Delarche F, Marquette C, Dardenne M, Haour F (1995) Localization and characterization of interleukin-1 receptors in the islets of Langerhans from control and nonobese diabetic mice. Endocrinology 136: 609-613
220. Bristulf J, Gatti S, Malinowsky D, Bjork L, Sundgren AK, Bartfai T (1994) Interleukin-1 stimulates the expression of type I and type II interleukin-1 receptors in the rat insulinoma cell line Rinm5F; sequencing a rat type II interleukin-1 receptor cDNA. Eur Cytokine Netw 5: 319-330
221. Eizirik DL, Tracey DE, Bendtzen K, Sandler S (1991) An interleukin-1 receptor antagonist protein protects insulin-producing beta cells against suppressive effects of interleukin-1β. Diabetologia 34: 445-448
222. Welsh N, Bendtzen K, Sandler S (1991) Influence of protease on inhibitory and stimulatory effects of interleukin 1β on β-cell function. Diabetes 40: 290-293
223. Rabuazzo AM, Buscema M, Caltabiano V, et al. (1995) Interleukin-1β inhibition of insulin release in rat pancreatic islets: possible involvement of G-proteins in the signal transduction pathway. Diabetologia 38: 779-784
224. Sjöholm Å (1991) Cytokines inhibit proliferation and insulin secretion by clonal rat insulinoma cells (RINm5F) non-synergistically and in a pertussis toxin-insensitive manner. Immunol Lett 30: 81-86
225. Helqvist S, Bouchelouche PN, Johannesen J, Nerup J (1990) Interleukin 1β increases the cytosolic free sodium concentration in isolated rat islets of Langerhans. Scand J Immunol 32: 53-58
226. Corbett JA, Sweelland M, Lancaster JR Jr, McDaniel ML (1993) A 1-hour pulse with IL-1β induces formation of nitric oxide and inhibits insulin secretion by rat islets of Langerhans: evidence for a tyrosine kinase signalling mechanism. FASEB J 7: 369-374
227. Corbett JA, Kwon G, Misko TR Rodi GP, McDaniel ML (1994) Tyrosine kinase involvement in IL-1β-induced expression of iNOS by β-cells purified from islets of Langerhans. Am J Physiol 267:C48-C54
228. Zawalich WS, Zawalich KC (1989) Interleukin 1 is a potent stimulator of islet insulin secretion and phosphoinositide hydrolysis. Am J Physiol 256:[Endocrinol Metab 19]E19-E24
229. 2 accumulation by isolated pancreatic islets. Diabetes 38: 1251-1257
230. Bleich D, Chen S, Gu J-L, et al. (1995) Interleukin-1β regulates the expression of a leukocyte type of 12-lipoxygenase in rat islets and RIN m5F cells. Endocrinology 136: 5736-5744
231. 2+ uptake by islets of Langerhans. FEBS Lett 248: 35-38
232. Helqvist S, Bouchelouche PN, Andersen HU, Nerup J (1989) Modulation of calcium flux influences interleukin 1β effects on insulin release from isolated islets of Langerhans. Acta Endocrinol 121: 447-455
233. 2+ handling. Acta Endocrinol 121: 698-704
234. Sandler S, Bendtzen K, Eizirik DL, Strandell E, Welsh M, Welsh N (1990) Metabolism and β-cell function of rat pancreatic islets exposed to human interleukin-1β in the presence of a high glucose concentration. Immunol Lett 26: 245-252
235. Hughes JH, Watson MA, Easom RA, Turk J, McDaniel ML (1990) Interleukin-1 induces rapid and transient expression of the c-fos proto-oncogene in isolated pancreatic islets and in purified β-cells. FEBS Lett 266: 33-36
236. Kwon G, Corbett JA, Rodi CP, Sullivan P, McDaniel ML (1995) Interleukin-1β-induced nitric oxide symhase expression by rat pancreatic β-cells: evidence for the involvement of nuclear factor kB in the signaling mechanism. Endocrinology 136: 4790-4795
237. Welsh N (1995) Interleukin-1β induced ceramide and diacylglycerol generation does not lead to NF-kB activation in RINm5F cells. Diabetologia 38:[Suppl 1]A82 (Abstract)
238. Eizirik DL, Sandler S, Welsh N, Juntti-Berggren L, Berggren P-O (1995) Interleukin-1β-induced stimulation of insulin release in mouse pancreatic islets is related to diacylglycerol production and protein kinase C activation. Mol Cell Endocrinol 111: 159-165
239. Zawalich WS, Diaz VA (1986) Interleukin 1 inhibits insulin secretion from isolated perifused rat islets. Diabetes 35: 1119-1123
240. Spinas GA, Hansen BS, Linde S et al. (1987) Interleukin 1 dose-dependently affects the biosynthesis of (pro)insulin in isolated rat islets of Langerhans. Diabetologia 30: 474-480
241. Comens PG, Wolf BA, Unanue ER, Lacy PE, McDaniel ML (1987) Interleukin 1 is potent modulator of insulin secretion from isolated rat islets of Langerhans. Diabetes 36: 963-970
242. Zawalich WS, Zawalich KC (1991) Influence of staurosporine, nitrendipine and monooleoylglycerol on interleukin-1-induced insulin secretion and phosphoinositide hydrolysis. Mol Cell Endocrinol 82: 303-311
243. Corbett JA, Kwon G, Turk J, McDaniel ML (1993) IL-1β induces coexpression of both nitric oxide synthase and cyclooxygenase by islets of Langerhans: activation of cyclooxygenase by nitric oxide. Biochemistry 32: 13767-13770
244. Sjöholm Å (1995) Ceramide inhibits pancreatic beta-cell insulin production and mitogenesis and mimics the actions of interleukin-1 beta. FEBS Lett 367: 283-286
245. Bigdeli N, Niemann A, Sandler S, Eizirik DL (1994) Dissociation between interleukin-1 beta induced expression of mRNA for superoxide dismutase and nitric oxide synthase in insulin-producing cells. Biochem Biophys Res Commun 203:1542-1547
246. Spinas GA, Palmer JP, Mandrup-Poulsen T, Andersen H, Nielsen JH, Nerup J (1988) The bimodal effect of interleukin 1 on rat pancreatic beta-cells - stimulation followed by inhibition - depends upon dose, duration of exposure, and ambient glucose concentration. Acta Endocrinol 119: 307-311
247. Mandrup-Poulsen T, Nerup J, Reimers JI et al. (1996) Cytokines and the endocrine system. II. Roles in substrate metabolism, modulation of thyroidal and pancreatic endocrine cell functions and autoimmune endocrine diseases. Eur J Endocrinol 134: 21-30
248. Eizirik DL, Sandler S, Hallberg A, Bendtzen K, Sener A, Malaisse WJ (1989) Differential sensitivity of β-cell secretagogues in cultured rat pancreatic islets exposed to human interleukin-1β. Endocrinology 125: 752-759
249. Southern C, Schulster D, Green IC (1990) Inhibition of insulin secretion by interleukin-1β and tumour necrosis factor-α via an L-arginine-dependent nitric oxide generating mechanism. FEBS Lett 276: 42-44
250. Welsh N, Eizirik DL, Bendtzen K, Sandler S (1991) Interleukin-1β-induced nitric oxide production in isolated rat pancreatic islets requires gene transcription and may lead to inhibition of the Krebs cycle enzyme aconitase. Endocrinology 129: 3167-3173
251. Corbett JA, Lancaster JR Jr, Sweetland MA, McDaniel ML (1991) Interleukin-1β-induced formation of EPR-detectable iron-nitrosyl complexes in islets of Langerhans. J Biol Chem 266: 21351-21354
252. Eizirik DL, Cagliero E, Björklund A, Welsh N (1992) Interleukin-1β induces the expression of an isoform of nitric oxide synthase in insulin-producing cells, which is similar to that observed in activated macrophages. FEBS Lett 308: 249-252
253. Karlsen AE, Andersen HU, Vissing H et al. (1995) Cloning and expression of cytokine-inducible nitric oxide synthase cDNA from rat islets of Langerhans. Diabetes 44: 753-758
254. Strandell E, Buschard K, Saldeen J, Welsh N (1995) Interleukin-1β induces the expression of HSP70, heme oxygenase and Mn-SOD in FACS-purified rat islet β-cells, but not in α-cells. Immunol Lett 48: 145-148
255. Lancaster JR Jr (1994) Simulation of the diffusion and reaction of endogenously produced nitric oxide. Proc Natl Acad Sci 91: 8137-8141
256. Kallmann B, Burkart V, Kröncke K-D, Kolb-Bachofen V, Kolb H (1992) Inflammatory damage of pancreatic islet cells by nitric oxide: protection by nicotinamide but not by radical scavengers. Life Sci 51: 671-678
257. Cunningham JM, Mabley JG, Delaney CA, Green IC (1994) The effect of nitric oxide donors on insulin secretion, cyclic GMP and cyclic AMP in rat islets of Langerhans and the insulin-secreting cell lines HIT-T15 and RINm5F. Mol Cell Endocrinol 102: 23-29
258. Fehsel K, Jalowy A, Qi S, Burkart V, Hartmann B, Kolb H (1993) Islet cell DNA is a target of inflammatory attack by nitric oxide. Diabetes 42: 496-500
259. Heller B, Wang Z-Q, Wagner EF et al. (1995) Inactivation of the poly (ADP-ribose) polymerase gene affects oxygen radical and nitric oxide toxicity in islet cells. J Biol Chem 270: 11176-11180
260. Xie K, Huang S, Zhongyun D, Fidler IJ (1993) Cytokine-induced apoptosis in transformed murine fibroblasts involves synthesis of endogenous nitric oxide. Int J Oncol 3: 1043-1048
261. Scaglia L, Smith FE, Bonner-Weir S (1995) Apoptosis contributes to the involution of β-cell mass in the post parturn rat pancreas. Endocrinology 136: 5461-5468
262. Sánchez-Margalet V, Lucas M, Solano F, Goberna R (1993) Sensitivity of insulin-secreting RIN m5F cells to undergoing apoptosis by the protein kinase C inhibitor staurosporine. Exp Cell Res 209: 160-163
263. Loweth AC, Scarpello JHB, Williams GT, Morgan NG (1995) Effects of modulators of G-protein function on apoptosis in RINm5F cells and rat islets. Diabetologia 38:[Suppl 1]A45 (Abstract)
264. Ankarcrona M, Dypbukt JM, Brüne B, Nicotera P (1994) Interleukin-1β-induced nitric oxide production activates apoptosis in pancreatic RINm5F cells. Exp Cell Res 213: 172-177
265. Morgan NG, Cable HC, Newcombe NR, Williams GT (1994) Treatment of cultured pancreatic B-cells with streptozotocin induces cell death by apoptosis. Biosci Rep 14: 243-250
266. Kaneto H, Fujii J, Seo HG et al. (1995) Apoptotic cell death triggered by nitric oxide in pancreatic β-cells. Diabetes 44: 733-738
267. Dunger A, Schlosser M, Ziegler B, Schmidt S (1995) Interleukin 1-beta induces apoptosis in insulin-producing cells. Diabetologia 38:[Suppl 1]A38 (Abstract)
268. Flodström M, Niemann A, Bedoya FJ, Morris SM, Eizirik DL (1995) Expression of the citrulline-nitric oxide cycle in rodent and human pancreatic β-cells: induction of argininosuccinate synthetase by cytokines. Endocrinology 136: 3200-3206
269. Kleemann R, Rothe H, Kolb-Bachofen V et al. (1993) Transcription and translocation of inducible nitric oxide synthase in the pancreas of prediabetic BB rats. FEBS Lett 328: 9-12
270. Rothe H, Faust A, Schade U et al. (1994) Cyclophosphamide treatment of female non-obese diabetic mice causes enhanced expression of inducible nitric oxide synthase and interferon-gamma, but not of interleukin-4. Diabetologia 37: 1154-1158
271. Lukic ML, Stosic-Grujicic S, Ostojic N, Chan WL, Liew FY (1991) Inhibition of nitric oxide generation affects the induction of diabetes by streptozocin in mice. Biochem Biophys Res Commun 178: 913-920
272. Corbett JA, Mikhael A, Shimizu J et al. (1993) Nitric oxide production in islets from nonobese diabetic mice: Aminoguanidine-sensitive and -resistant stages in the immunological diabetic process. Proc Natl Acad Sci 90: 8992-8995
273. G-Nitro-L-Arginine methyl ester reduces the incidence of IDDM in BB/E rats. Diabetes 44: 365-368
274. Suarez-Pinzon WL, Strynadka K, Schulz R, Rabinovitch A (1994) Mechanisms of cytokine-induced destruction of rat insulinoma cells: the role of nitric oxide. Endocrinology 134: 1006-1010
275. Cetkovic-Cvrlje M, Sandler S, Eizirik DL (1993) Nicotinamide and dexamethasone inhibit interleukin-1-induced nitric oxide production by RINm5F cells without decreasing messenger ribonucleic acid expression for nitric oxide synthase. Endocrinology 133: 1739-1743
276. Andersen HU, Jørgensen KH, Egeberg J, Mandrup-Poulsen T, Nerup J (1994) Nicotinamide prevents interleukin-1 effects on accumulated insulin release and nitric oxide production in rat islets of Langerhans. Diabetes 43: 770-777
277. Corbett JA, Sweetland M, Wang JL, Lancaster JR Jr, McDaniel ML (1993) Nitric oxide mediates cytokine-induced inhibition of insulin secretion by human islets of Langerhans. Proc Natl Acad Sci 90: 1731-1735
278. Eizirik DL, Sandler S, Welsh N, et al. (1994) Cytokines suppress human islet function irrespective of their effects on nitric oxide generation. J Clin Invest 93: 1968-1974
279. Delaney CA, Eizirik DL, Lowe JE et al. (1995) Effects of nitric oxide on DNA damage and ultrastructure in islets of Langerhans - a comparison of human and rodent. Diabetologia 38:[Suppl 1]A17 (Abstract)
280. Sumoski W, Baquerizo H, Rabinovitch A (1989) Oxygen free radical scavengers protect rat islet cells from damage by cytokines. Diabetologia 32: 792-796
281. Takane N, Yamada K, Inada C, Nonaka K (1994) Cytokine-induced Fas antigen mRNA expression and DNA fragmentation in islet cells. 15th International Diabetes Federation Congress, Kobe, Japan, 1994
282. Hughes JH, Colca JR, Easom RA, Turk J, McDaniel ML (1990) Interleukin 1 inhibits insulin secretion from isolated rat pancreatic islets by a process that requires gene transcription and mRNA translation. J Clin Invest 86: 856-863
283. Eizirik DL, Bendtzen K, Sandler S (1991) Short exposure of rat pancreatic islets to interleukin-1β induces a sustained but reversible impairment in β-cell function: influence of prolease activation, gene transcription, and protein synthesis. Endocrinology 128: 1611-1616
284. Andersen HU, Larsen PM, Fey SJ, Karlsen AE, Mandrup-Poulsen T, Nerup J (1995) Two-dimensional gel electrophoresis of rat islet proteins. Interleukin 1β-induced changes in protein expression are reduced by L-Arginine depletion and nicotinamide. Diabetes 44: 400-407
285. Helqvist S, Polla BS, Johannesen J, Nerup J (1991) Heat shock protein induction in rat pancreatic islets by recombinant human interleukin 1β. Diabetologia 34: 150-156
286. Borg LAH, Cagliero E, Sandler S, Welsh N, Eizirik DL (1992) Interleukin-1β increases the activity of superoxide dismutase in rat pancreatic islets. Endocrinology 130: 2851-2857
287. Eizirik DL, Strandell E, Bendtzen K, Sandler S (1988) Functional characteristics of rat pancreatic islets maintained in culture after exposure to human interleukin 1. Diabetes 37: 916-919
288. Cetkovic-Cvrlje M, Eizirik DL (1994) TNF-α and IFN-gamma potentiate the deleterious effects of IL-1β on mouse pancreatic islets mainly via generation of nitric oxide. Cytokine 6: 399-406
289. Yamada K, Otabe S, Inada C, Takane N, Nonaka K (1993) Nitric oxide and nitric oxide synthase mRNA induction in mouse islet cells by interferon-gamma plus tumor necrosis factor-α. Biochem Biophys Res Commun 197: 22-27
290. Sternesjö J, Bendtzen K, Sandler S (1995) Effects of prolonged exposure in vitro to interferon-gamma and tumour necrosis factor-α on nitric oxide and insulin production of rat pancreatic islets. Autoimmunity 20: 185-190
291. Nerup J, Mandrup-Poulsen T, Mølvig J, Helqvist S, Wogensen LD, Egeberg J (1988) Mechanisms of pancreatic β-cell destruction in type I diabetes. Diabetes Care 11:[Suppl 1]16-23
292. Dahlquist G (1995) Environmental risk factors in human type 1 diabetes - an epidemiological perspective. Diab Metab Rev 11: 37-46
293. Leiter E (1987) Murine macrophages and pancreatic beta-cells. Chemotactic properties of insulin and beta-cytostatic action of interleukin-1. J Exp Med 166: 1174-1179
294. Cavallo MG, Baroni MG, Toto A et al. (1992) Viral infection induces cytokine release by beta islet cells. Immunology 75: 664-668
295. Bach LW (1996) Interleukin-1β-mediated beta-cell inhibition in vivo. A role of circulating interleukin-1β in the pathogenesis of insulin dependent diabetes mellitus? Dan Med Bull 43: 39-57
296. Tsumara H, Wang JZ, Ogawa S, Ohota H, Komada H, Ito Y et al. (1994) IL-1 induces intracisternal type A virus and retrovirus type C in pancreatic beta-cells of NOD mice. J Exp Anim Sci 36: 141-150
297. Takane N, Yamada K, Otabe S, Inoue M, Nonaka K (1993) Interleukin-1 induction of tumor necrosis factor-α mRNA and bioactive tumor necrosis factor-α in a pancreatic β-cell line by a mechanism requiring no de novo protein synthesis. Biochem Biophys Res Commun 194: 163-169
298. Campbell IL, Cutri A, Wilson A, Harrison LC (1989) Evidence for IL-6 production by and effects on the pancreatic β-cell. J Immunol 143: 1188-1191
299. Campbell IL, Cutri A, Wilkinson D, Boyd AW, Harrison LC (1989) Intercellular adhesion molecule 1 is induced on isolated endocrine islet cells by cytokines but not by reovirus infection. Proc Natl Acad Sci 86: 4282-4286
300. Kjaer TW, Rygaard J, Bendtzen K, Josefsen K, Bock T, Buschard K (1992) Interleukins increase surface ganglioside expression of pancreatic islet cells in vitro. APMIS 100: 509-514
301. Eizirik DL, Welsh N, Niemann A, Velloso LA, Malaisse WJ (1994) Succinic acid monomethyl ester protects rat pancreatic islet secretory potential against interleukin-1β (IL-1β) without affecting glutamate decarboxylase expression or nitric oxide production. FEBS Lett 337: 298-302
302. Feutren G, Papoz L, Assan R et al. (1986) Cyclosporin increases the rate and length of remissions in insulin-dependent diabetes of recent onset. Results of a multicentre double-blind trial. Lancet ii:119-123
303. The Canadian-European randomized control trial group (1988) Cyclosporin-induced remission of IDDM after early intervention. Association of 1 yr of cyclosporin treatment with enhanced insulin secretion. Diabetes 37: 1574-1582
304. Mori Y, Suko M, Okudaira H et al. (1986) Preventive effects of cyclosporin on diabetes in NOD mice. Diabetologia 29: 244-247
305. Laupacis A, Stiller CR, Gardell C et al. (1983) Cyclosporin prevents diabetes in BB Wistar rats. Lancet i:10-12
306. Lukic M, Stosic S, Ostojic N (1993) Effector mechanisms in low-dose streptozotocin induced diabetes in mice. EOS 13: 91-92
307. Welsh N, Bendtzen K, Welsh M (1995) Expression of an insulin/interleukin-1 receptor antagonist hybrid gene in insulin-producing cell lines (HIT-T15 and NIT-1) confers resistance against interleukin-1-induced nitric oxide production. J Clin Invest 95: 1717-1722
308. Welsh N (1994) A role for tyrosine kinase activation in interleukin-1 beta induced nitric oxide production in the insulin producing cell line RINm-5F. Biosci Rep 14: 43-50
309. Saldeen J, Welsh N (1994) Interleukin-1β induced activation of NF-kB in insulin producing RINm5F cells is prevented by the protease inhibitor Nα-p-tosyl-1-lysine chromethylketone. Biochem Biophys Res Commun 203: 149-155
310. Bedoya FJ, Flodström M, Eizirik DL (1995) Pyrrolidine dithiocarbamate prevents IL-1-induced nitric oxide synthase mRNA, but not superoxide dismutase mRNA, in insulin producing cells. Biochem Biophys Res Commun 210: 816-822
311. Kolb H, Kiesel U, Kröncke K-D, Kolb-Bachofen V (1991) Suppression of low dose streptozotocin induced diabetes in mice by administration of a nitric oxide synthase inhibitor. Life Sci 49:PL 213-PL 217
312. G-Monomethyl-L-Arginine on the onset of diabetes in the spontaneously diabetic BB rat. Diabetes 44: 360-364
313. Yamada K, Inada C, Otabe S, Takane N, Hayashi H, Nonaka K (1993) Effects of free radical scavengers on cytokine actions on islet cells. Acta Endocrinol 128: 379-384
314. Drash AL, Rudert WA, Borquaye S, Wang R, Lieberman I (1988) Effect of probucol on development of diabetes mellitus in BB rats. Am J Cardiol 62: 27B-30B
315. Mendola J, Wright JR, Lacy PE (1989) Oxygen free-radical scavengers and immune destruction of murine islets in allograft rejection and multiple low-dose streptozocin-induced insulitis. Diabetes 38: 379-385
316. Mandrup-Poulsen T, Reimers JI, Andersen HU, et al. (1993) Nicotinamide treatment in the prevention of insulin-dependent diabetes mellitus. Diab Metab Rev 9: 295-309