Summary
Diabetes-prone BioBreeding (DPBB) rats were fed a diabetogenic, mainly plant-based rodent diet, Purina Chow 5001, or a diabetes-retardant, hydrolysed casein-based diet. The expression of MHC class I antigens on pancreatic beta cells occurred at around 25 days of age in Purina Chow-fed rats, and progressively increased with the length of time of feeding with the Purina diet. Most of the Purina Chow-fed DPBB rats revealed hyperexpression of MHC class I antigens on their pancreatic beta cells by 50 days of age. Approximately 92% of the hyperexpressed Purina Chow-fed DPBB rats developed severe insulitis and diabetes. In contrast, the majority of hydrolysed casein-fed DPBB rats did not show MHC class I antigen hyperexpression and these rats failed to develop insulitis or diabetes. Purina Chow-fed Wistar-Furth rats and diabetes-resistant BioBreeding (DRBB) rats showed only very weak background staining for MHC class I antigens on their beta cells. When Purina Chow-fed DPBB rats were treated with silica to inhibit macrophage infiltration into the pancreatic islets, the hyperexpression of MHC class I antigens was seen even more clearly, as beta cells remained intact. MHC class II antigens were not detected on pancreatic beta cells from DPBB, DRBB or Wistar-Furth rats, regardless of their diet. On the basis of these observations, we concluded that hyperexpression of MHC class I antigens on pancreatic beta cells was mainly restricted to Purina Chow-fed DPBB rats and that suppression of non-macrophage-dependent MHC class I antigen hyperexpression on pancreatic beta cells by a hydrolysed casein-based diet resulted in the prevention of insulitis and diabetes.
Article PDF
Similar content being viewed by others
Abbreviations
- DPBB rat:
-
diabetes-prone BioBreeding rat
- DRBB rat:
-
diabetes-resistant BioBreeding rat
- NOD mouse:
-
non-obese diabetic mouse
- HC:
-
hydrolysed casein-based, semi-purified diet
- PC:
-
Purina Chow 5001 non-purified, cereal-based diet
- WF rat:
-
Wistar-Furth rat
- MHC:
-
major histocompatibility complex
- IDDM:
-
insulin-dependent diabetes mellitus
- PBS:
-
phosphate buffered saline
References
Crisá L, Mordes JP, Rossini AA (1992) Autoimmune diabetes mellitus in the BB rat. Diabetes Metab Rev 8: 9–37
Marliss EB (ed) (1983) The Juvenile Diabetes Foundation Workshop on the spontaneously diabetic BB rat: its potential for insight into human juvenile diabetes. Metab Clin Exp 32[Suppl 1]:1–166
Parfrey NA, Prud'homme GJ, Colle E, Fuks A, Seemayer TA, Guttmann RD. (1989) Immunologic and genetic studies of diabetes in the BB rat. Crit Rev Immunol 9: 45–65
Scott FW, Sarwar G, Cloutier HE (1988) Diabetogenicity of various protein sources in the diet of the BB rat. In: Camerini-Davalos RA, Cole HS (eds) Prediabetes. Plenum Press, New York, pp 277–285
Scott FW, Elliott RB, Kolb H (1989) Diet and autoimmunity: prospect of prevention of type 1 diabetes. Diabetes, Nutrition and Metabolism 2: 61–73
Scott FW, Marliss EB (1991) Conference summary: diet as an environmental factor in development of IDDM. Can J Physiol Pharmacol 69: 311–319
Elliott RB, Martin JM (1984) Dietary protein: a trigger of insulin-dependent diabetes in the BB rat? Diabetologia 26: 297–299
Hoorfar J, Buschard K, Dagnaes-Hansen F (1993) Prophylactic nutritional modification of the incidence of diabetes in autoimmune non-obese diabetic (NOD) mice. Br J Nutr 69: 597–607
Issa-Chergui D, Guttmann RD, Seemayer TA, Kelley VE, Colle EC (1988) The effect of diet on the spontaneous insulin-dependent diabetic syndrome in the rat. Diabetes Res 9: 81–86
Bieri JG, Stoewsand GS, Briggs GM, Phillips RW, Woodward JC, Knapka JJ (1977) Report of the American Institute of Nutrition ad hoc committee on standards for nutritional studies. J Nutr 107: 1340–1348
Bieri JG (1980) Second report of the ad hoc committee on standards for nutritional studies. J Nutr 110: 1726
Scott FW (1994) Food, diabetes and immunology. In: Forse RA, Bell SJG, Blackburn L, Kabbash L (eds) Diet, nutrition and immunology. CRC Press, Boca Raton, Florida, pp 71–92
Hoorfar J, Scott FW, Cloutier HE (1991) Dietary plant materials and development of diabetes in the BB rat. J Nutr 121: 908–916
Campbell RD, Milner CM (1993) MHC genes in autoimmunity. Curr Op Immunol 5: 887–893
Dean BM, Walker R, Bone AJ, Baird JD, Cooke A (1985) Pre-diabetes in the spontaneously diabetic BB/E rat: lymphocyte subpopulations in the pancreatic infiltrate and expression of rat MHC class II molecules in endocrine cells. Diabetologia 28: 464–466
Weringer E, Like AA (1988) Identification of T cell subsets and class I and class II antigen expression in islet grafts and pancreatic islets of diabetic BioBreeding/Worcester rats. Am J Pathol 132: 292–303
Markmann JF, Schachner MS, Bassiri H, Barker CF, Naji A (1990) The contribution of MHC modulation to islet allograft rejection. Horm Metab Res 25S:104–108
Osorio RW, Ascher NL, Jaenisch R et al. (1993) Major histocompatibility complex class I deficiency prolongs islet allograft survival. Diabetes 42: 1520–1527
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
Lee KU, Pak CY, Amano K, Yoon JW (1988) Prevention of lymphocytic thyroiditis and insulitis in diabetes-prone BB rats by the depletion of macrophages. Diabetologia 31: 400–402
Lee KU, Kim MK, Amano K et al. (1988) Preferential infiltration of macrophages in the early stages of insulitis precedes the involvement of activated T-lymphocytes in the spontaneously diabetic BB rat. Diabetes 31: 1053–1058
Elliott RB, Reddy SN, Bibby NJ, Kida K (1988) Dietary prevention of diabetes in the non-obese diabetic mouse. Diabetologia 31: 62–64
Yoon JW (1995) Environmental factors in the pathogenesis of insulin dependent diabetes mellitus. In: Pickup J, Williams G (eds) Text book of diabetes. Blackwell, London, (in press)
Scott FW, Hoorfar J, Cloutier HE (1990) Lymphocytes and macrophages in BB rats fed diabetes-retardant or promoting diets. In: Shafrir E (ed) Frontiers in diabetes research: lessons from animal diabetes III. Smith-Gordon, London pp 192–194
Ono SJ, Issa-Chergui B, Colle E, Guttmann RD, Seemayer TA, Fuks A (1988) IDDM in BB rats: enhanced MHC class I heavy-chain gene expression in pancreatic islets. Diabetes 37: 1411–1418
Oschilewski U, Kiesel U, Kolb H (1985) Administration of silica prevents diabetes in BB rats. Diabetes 34: 197–199
Bottazzo GF, Dean BM, McNally JM, Mackay EH, Swift PGF, Gamble DR (1985) In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas of diabetic insulitis. N Engl J Med 313: 353–360
Foulis AK, Farquharson MA, Hardman R (1987) Aberrant expression of class II major histocompatibility complex molecules by B cells and hyperexpression of class I major histocompatibility complex molecules by insulin containing islets in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 30: 333–343
Hart DNJ, Newton MR, Reece-Smith H, Fabre JW, Morris PJ (1983) Major histocompatibility complex antigens in the rat pancreas, isolated pancreatic islets, thyroid and adrenal. Transplantation 36: 431–435
Issa-Chergui B, Yale JF, Vigeant C, Seemayer TA (1988) Major histocompatibility complex gene product expression on pancreatic Β cells in acutely diabetic BB rats. Am J Pathol 30: 156–162
Yoon JW, Ihm SH, Lee KU, Amano K, Pak CY (1988) The initial step in the development of organ specific autoimmune disease in BB rats, Diabetologia 31: 779–780 (Letter)
In't Veld PA, Pipeleers DG (1988) In-situ characterization of pancreatic islets in rats developing diabetes, appearance of nonendocrine cells with surface MHC class II antigens and cytoplasmic insulin reactivity. J Clin Invest 82: 1123–1128
Allison J, Campbell IL, Morahan G, Mandel TE, Harrison LC, Miller JFAP (1988) Diabetes in transgenic mice resulting from over-expression of class I histocompatibility molecules in pancreatic Β-cells. Nature 333: 529–533
Hayakawa M, Yokono K, Nagata M et al. (1991) Morphological analysis of selective destruction of pancreatic beta cells by cytotoxic T lymphocytes in NOD mice. Diabetes 40: 1210–1217
Leiter EH, Christianson GJ, Serreze DV, Ting AT, Worthen S (1989) MHC antigen induction by interferon-γ on cultured mouse pancreatic Β cells and macrophages, genetic analysis of strain differences and discovery of an “occult” class I-like antigen in NOD/Lt mice. J Exp Med 170: 1243–1262
Serreze DV, Gaskins HR, Leiter EH (1993) Defects in the differentiation and function of antigen presenting cells in NOD/Lt mice. J Immunol 150: 2534–2543
Taki T, Nagata M, Ogawa W et al. (1991) Prevention of cyclophosphamide-induced and spontaneous diabetes in NON/Shi/Kbe mice by anti-class I Kd monoclonal antibody. Diabetes 40: 1203–1209
Stock PG, Ascher NL, Chen S, Bumgardner GL, Field MJ, Sutherland ER (1989) Modulation of MHC class I antigen decrease pancreatic islet immunogenicity. J Surg Res 46: 317–321
Katz J, Benoist C, Mathis D (1993) Major histocompatibility complex class I molecules are required for the generation of insulitis in non-obese diabetic mice. Eur J Immunol 23: 3358–3360
McInerney MF, Rath S, Janeway CA (1991) Exclusive expression of MHC class II proteins on CD45+ cells in pancreatic islets of NOD mice. Diabetes 40: 648–651
Edouard P, Hiserodt JC, Plamondon C, Poussier P (1993) CD8+ T-cells are required for adoptive transfer of the BB rat diabetic syndrome. Diabetes 42: 390–397
Bellgrau D, Lagarde AC (1990) Cytotoxic precursors with low level CD8 in the diabetes-prone Biobreeding rat: implications for generation of an autoimmune T-cell repertoire. PNAS 87: 313–317
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Li, X.B., Scott, F.W., Park, Y.H. et al. Low incidence of autoimmune type I diabetes in BB rats fed a hydrolysed casein-based diet associated with early inhibition of non-macrophage-dependent hyperexpression of MHC class I molecules on beta cells. Diabetologia 38, 1138–1147 (1995). https://doi.org/10.1007/BF00422362
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00422362