Horm Metab Res 2004; 36(9): 585-594
DOI: 10.1055/s-2004-825920
Review
© Georg Thieme Verlag KG Stuttgart · New York

Insulin-dependent Diabetes and Gut Dysfunction: The BB Rat Model

W.  J.  Malaisse1 , P.  Courtois1 , F.  W.  Scott2
  • 1Laboratory of Experimental Hormonology, Brussels Free University, Brussels, Belgium
  • 2Ottawa Health Research Institute, Ottawa, Canada
Further Information

Publication History

Received 12 February 2004

Accepted after revision 24 March 2004

Publication Date:
15 October 2004 (online)

Abstract

Accumulating data indicate that intestinal dysfunction and dysregulation of the gut immune system may play a role in the development of type 1 diabetes. This review deals with the occurrence of gut damage and dysfunction in BB rats, an animal model of spontaneous immune type 1 diabetes, placing special emphasis on the effect of diet on the incidence of diabetes in BB rats, the identification of a type 1 diabetes-related protein from wheat, and preliminary observations documenting anomalies in the inductive tissues of the gut immune system (Peyer's patch cells and mesenteric lymph node cells) and pancreatic lymph node cells of diabetes-prone BB rats. In addition to histological evidence of gut damage, the review will also draw attention to altered intestinal disaccharidase activity, changes in intestinal peroxidase activity, glucagon-like peptide 1 anomalies, and perturbation of both intestinal permeability and mucin content in BB rats. In all these cases, the findings in rats fed a diabetes-promoting diet are compared to those collected in animals receiving a protective diabetes-retardant diet.

References

  • 1 Vaarala O. Gut and the induction of immune tolerance in type 1 diabetes.  Diabetes Metab Res. 1999;  Rev 15 353-361
  • 2 Vaarala O. The gut immune system and type 1 diabetes.  Ann NY Acad Sci. 2002;  958 39-46
  • 3 Bao F, Yu L, Babu S, Wang T, Hoffenberg E J, Rewers M, Eisenbarth G S. One third of HLA DQ2 homozygous patients with type 1 diabetes express celiac disease-associated transglutaminase autoantibodies.  J Autoimmun. 1999;  13 143-148
  • 4 Lampasona V, Bonfanti R, Bazzigaluppi E, Venerando A, Chiumello G, Bosi E, Bonifacio E. Antibodies to tissue transglutaminase C in Type 1 diabetes.  Diabetologia. 1999;  42 1195-1198
  • 5 Kiemetti P, Savilahti E, Ilonen J, Akerblom H K, Vaarala O. T-cell reactivity to wheat gluten in patients with insulin-dependent diabetes mellitus.  Scand J Immunol. 1998;  47 48-53
  • 6 Catassi C, Guerrieri A, Bartolotta E, Coppa G V, Giorgi P L. Antigliadin antibodies at onset of diabetes in children. Lancet ii 1987: 158
  • 7 Volta U, Bonazzi C, Pisi F, Salardi S, Cacciari E. Antigliadin and antireticulin antibodies in coeliac disease and at onset of diabetes in children. Lancet ii 1987: 1034-1035
  • 8 MacFarlane A J, Scott F W. Environmental factors and type 1 diabetes. In: Pickup JC, Williams G, (eds.) Textbook of diabetes. Oxford; Blackwell Publishing 2002: 17.1-17.16
  • 9 Westerholm-Ormio M, Vaarala O, Pihkala P, Ilonen J, Savilahti E. Immunological activity in the small intestinal mucosa of pediatric patients with type 1 diabetes.  Diabetes. 2003;  52 2287-2295
  • 10 Norris J M, Barriga K, Klingensmith G, Hoffman M, Eisenbarth G S, Erlich H A, Rewers M. Timing of initial cereal exposure in infancy and risk of islet autoimmunity.  J Am Med Assoc. 2003;  290 1713-1720
  • 11 Ziegler A-G, Schmid S, Huber D, Hummel M, Bonifacio E. Early infant feeding and risk of developing type 1 diabetes-associated autoantobodies.  J Am Med Assoc. 2003;  290 1721-1728
  • 12 Atkinson M, Gale E AM. Infant diets and type 1 diabetes: too early, too late, or just too complicated?.  J Am Med Assoc. 2003;  290 1771-1772
  • 13 Rossini A A, Williams R M, Mordes J P, Appel M C, Like A A. Spontaneous diabetes in the gnotobiotic BB/W rat.  Diabetes. 1979;  28 1031-1032
  • 14 Beales P E, Elliott R B, Flohé S, Hill J P, Kolb H, Pozzilli P, Wang G-S, Wasmuth H, Scott F W. A multi-centre, blinded international trial of the effect of A1 and A2 β-casein variants on diabetes incidence in two rodent models of spontaneous Type I diabetes.  Diabetologia. 2002;  45 1240-1246
  • 15 Scott F W. Food-induced type 1 diabetes in the BB rats.  Diabetes/Metab Rev. 1996;  12 341-359
  • 16 Akerblom H K, Knip M. Putative environmental factors in Type 1 diabetes.  Diabetes/Metab Rev. 1998;  14 31-67
  • 17 MacFarlane A J, Burghardt K M, Kelly J, Simell T, Simell O, Altosaar I, Scott F W. A type 1 diabetes-related protein from wheat (Triticum aestivum). cDNA clone of a wheat storage globulin, Glb1, linked to islet damage.  J Biol Chem. 2003;  278 54-63
  • 18 Scott F W, Olivares E, Sener A, Malaisse W J. Dietary effects on insulin and nutrient metabolism in mesenteric lymph node cells, splenocytes, and pancreatic islets of BB rats.  Metabolism. 2000;  49 1111-1117
  • 19 Malaisse W J, Olivares E, Laghmich A, Ladrière L, Sener A, Scott F W. Feeding a protective hydrolyzed casein diet to young diabetes-prone BB rats affects oxidation of L-[U-14C]glutamine in islets and Peyer's patches, reduces abnormally high mitotic activity in mesenteric lymph nodes, enhances islet insulin and tends to normalize NO production.  Int J Exp Diab Res. 2000;  1 121-130
  • 20 Olivares E, Ladrière L, Laghmich A, Sener A, Malaisse W J, Scott F W. Effects of a protective hydrolyzed casein diet upon the metabolic and secretory responses of pancreatic islets to IL-1β, cytokine production by mesenteric lymph node cells, mitogenic and biosynthetic activities in Peyer's patch cells, and mitogenic activity in pancreatic lymph node cells from control and diabetes-prone BB rats.  Mol Gen Metab. 1999;  68 379-390
  • 21 Graham S, Courtois P, Malaisse W J, Rozing J, Mowat A M, Scott F W. Enteropathy precedes type 1 diabetes in the BB rat.  Gut. 2004;  53 in press
  • 22 Hardin J A, Donegan L, Woodman R C, Trevenen C, Gall D G. Mucosal inflammation in a genetic model of spontaneous type I diabetes mellitus.  Can J Physiol Pharmacol. 2002;  80 1064-1070
  • 23 Miller O, Crane R K. The digestive function of the epithelium of small intestine. II. Localization of disaccharide hydrolysis in the isolated brush border portion of intestinal epithelial cells.  Biochim Biophys Acta. 1961;  52 293-298
  • 24 Semenza G, Aurichio S. Small intestinal disaccharidases. In: Scriver CR, Beaudet AL, Sly WS, Valle DS (eds.) The metabolic and molecular bases of intestinal diseases. New York; McGraw-Hill 1995: 4451-4480
  • 25 Courtois P, Meuris S, Sener A, Malaisse W J, Scott F W. Invertase, maltase, lactase, and peroxidase activities in duodenum of BB rats.  Endocrine. 2002;  19 293-299
  • 26 Nakabou Y, Ishikawa Y, Misake A, Hagihira H. Effect of food intake on intestinal absorption and mucosal hydrolases in alloxan diabetic rats.  Metabolism. 1980;  29 181-185
  • 27 Younoszai M K, Schedl H P. Effect of diabetes on intestinal disaccharidase activities.  J Lab Clin Med. 1972;  79 579-586
  • 28 Olsen W A, Korsmo H. Enhancement of intestinal sucrase activity in experimental diabetes: the role of intraluminal factors.  J Lab Clin Med. 1975;  85 823-837
  • 29 Younoszai M K, Ranshaw J. Intestinal disaccharidases in the rat: effects of pregnancy and diabetes.  J Nutr. 1976;  106 504-508
  • 30 Olsen W A, Rogers L. Jejunal sucrase activity in diabetic rats.  J Lab Clin Med. 1971;  77 838-842
  • 31 O'Grady J G, Stevens F M, Keane R, Cryan E M, Egan-Mitchell B, McNicholl B, McCarthy C F, Fottrell P F. Intestinal lactase, sucrase, and alkaline phosphatase in 373 patients with coeliac disease.  J Clin Pathol. 1984;  37 298-301
  • 32 Murray I A, Smith J A, Coupland K, Ansell I D, Long R G. Intestinal disaccharidase deficiency without villous atrophy may represent early coeliac disease.  Scand J Gastroenterol. 2001;  36 163-168
  • 33 Nieminen U, Kahri A, Savilahti E, Färkkilä M A. Duodenal disaccharidase activities in the follow-up of villous atrophy in coeliac disease.  Scand J Gastroentrol. 2001;  36 507-510
  • 34 Malaisse W J, Courtois P, Sener A, Scott F W. Intestinal disaccharidase activity in Wistar-Furth and BioBreeding rats.  Diab Metab. 2003;  29 (suppl 2) 4S160 (abstract)
  • 35 Courtois P, Sener A, Scott F W, Malaisse W J. Disaccharidase activity in the intestinal tract of Wistar-Furth, BBc and BBdp rats.  Brit J Nutr. 2004;  91 201-209
  • 36 Courtois P, Sener A, Scott F W, Malaisse W J. Peroxidase activity in the intestinal tract of Wistar-Furth and BB rats.  Diabetes/Metab Res Rev. 2004;  20 305-314
  • 37 Bozeman P M, Learn D B, Thomas E L. Assay of the human leukocyte enzymes myeloperoxidase and eosinophil peroxidase.  J Immun Meth. 1990;  126 125-133
  • 38 Drucker D J. Biological actions and therapeutical potential of the glucagon-like peptides.  Gastroenterology. 2002;  122 531-544
  • 39 Malaisse W J, Valverde I, Redondo A, Acitores A, Villanueva-Peñacarrillo M L, Meuris S, Courtois P, Sener A, Scott F W. Glucagon-like peptide 1 content of the intestinal tract in BB rats.  Diabetes. 2002;  51 (suppl 2) A580 (abstract)
  • 40 Lüttichau H R, Van Solinge W W, Nielsen F C, Rehfeld J F. Development expression of the gastrin and cholecystokinin genes in rat colon.  Gastroenterology. 1993;  104 1092-1098
  • 41 Cancelas J, Sancho V, Villanueva-Peñacarrillo M L, Courtois P, Scott F W, Valverde I, Malaisse W J. Glucagon-like peptide 1 content of intestinal tract in adult rats injected with streptozotocin either during neonatal period or 7 d before sacrifice.  Endocrine. 2002;  19 279-286
  • 42 Kreymann B, Yiangou Y, Kanse S, Williams G, Ghatei M A, Bloom S R. Isolation and characterization of GLP-1 7-36 amide from rat intestine.  FEBS Lett. 1998;  242 167-170
  • 43 Brubaker P L, So D CY, Drucker D J. Tissue-specific differences in the levels of proglucagon-derived peptides in streptozotocin-induced diabetes.  Endocrinology. 1989;  124 3003-3009
  • 44 Valverde I, Wang G-S, Burghardt K, Kauri L M, Redondo A, Acitores A, Villanueva-Peñacarrillo M L, Courtois P, Sener A, Cancelas J, Malaisse W J, Scott F W. Bioactive GLP-1 in gut, receptor expression in pancreas and insulin response to GLP-1 in diabetes-prone rats.  Endocrine. 2004;  23 77-84
  • 45 Meddings J B, Jarand J, Urbanski S J, Hardin J, Gall D G. Increased gastrointestinal permeability is an early lesion in the spontaneously diabetic BB rat.  Am J Physiol. 1999;  276 G951-G957
  • 46 Courtois P, Jijakli H, Sener A, Scott F W, Malaisse W J. Effect of diet upon gut permeability and intestinal mucin content in diabetes-resistant and diabetes-prone BB rats.  Diab Metab. 2003;  29 (suppl 2) 4S160 (abstract)
  • 47 Mowat A M. Basic mechanism and clinical implications of oral tolerance.  Current Opinion Gastroenterol. 1999;  15 546-556
  • 48 Malaisse W J, Courtois P. Le diabète de type 1: une enteropathie?.  Bull Mem Acad Roy Med Belgique. 2003;  158 199-206

1 All quantitative data mentioned in this report refer to the mean values (±SEM), together with the number (n) of individual observations or experiments or corresponding degree of freedom (d.f.).

Prof. W. J. Malaisse

Laboratory of Experimental Hormonology, Brussels Free University

808 Route de Lennik · B-1070 Brussels · Belgium

Email: malaisse@ulb.ac.be

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