Spontaneous Autoimmune Diabetes mellitus in the BioBreeding/Worcester Rat

Like, Arthur A.; Rossini, A A

doi:10.1159/000156921

Cited by 40 publications

(42 citation statements)

References 31 publications

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“…Like human IDDM, the onset of clinical symptoms in diabetes-prone (BB/DP) BB rats appear during adolescence, generally between 60 and 120 days of age (Butler et al, 1983;Chappel and Chappel, 1983). These are characterized by rapid weight loss, polyuria, polydipsia, ketonuria, and finally death unless exogenous insulin is administered (Chappel and Chappel, 1983;Like and Rossini, 1984). The incidence of diabetes through 120 days of age is 60 -90% in most colonies and averaged 86% in a viral antibody-free NIH colony in Worcester, Massachusetts (Crisa et al, 1992).…”

Section: Abstract: Diabetes; Glomerular Basement Membrane Thickness;mentioning

confidence: 99%

Significant glomerular basement membrane thickening in hyperglycemic and normoglycemic diabetic‐prone BB Wistar rats

et al. 2004

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The diabetic-prone BioBreeding Wistar rat (BB/DP) is an autoimmune model of insulindependent diabetes mellitus. Approximately 80 -90% of the animals are hyperglycemic (BB/ DP h ) by 90 -120 days of age while those that do not become diabetic in adolescence (BB/DP n ) remain normoglycemic for life. Likewise, rats in the diabetes-resistant (BB/DR) strain are normoglycemic. Although renal morphological studies have been carried out in this model, ultrastructural observations of age-and diabetes-related extracellular matrix (ECM) changes, including glomerular basement membrane (GBM) morphometry, are not available. Moreover, possible renal changes in the relatively uncommon BB/DP n control animals have not been reported. The current electron microscopic study was carried out to investigate temporal changes in detergent-treated acellular ECM in BB/DP h rats at 2 weeks, 3 months, 6 months, and 1 year postonset of moderate hyperglycemia. Age-matched BB/DR and BB/DP n control animals were also examined. Our data demonstrate age-and diabetes-related alterations in mesangial matrix distributions and GBM widths and show for the first time significant increases in GBM thickening in both hyperglycemic (BB/DP h ) and normoglycemic (BB/DP n ) rats when compared to age-matched BB/DR controls. Surprisingly, the rate of increase is greatest in BB/DP n animals. Although the pathogenesis of diabetic basement membrane disease is not completely understood, GBM thickening is widely regarded as a morphological consequence of hyperglycemia. However, data in the current investigation show that ECM alterations, including significantly increased GBM thickness, may occur in genetically diabetic animals in the absence of hyperglycemia. © 2004 Wiley-Liss, Inc. Key words: diabetes; glomerular basement membrane thickness; BB Wistar ratsThe BioBreeding Wistar rat (BB rat) is an autoimmune model of insulin-dependent diabetes mellitus (IDDM) discovered in 1974 in a colony of pathogen-free Wistar rats (Chappel and Chappel, 1983). Like human IDDM, the onset of clinical symptoms in diabetes-prone (BB/DP) BB rats appear during adolescence, generally between 60 and 120 days of age (Butler et al., 1983;Chappel and Chappel, 1983). These are characterized by rapid weight loss, polyuria, polydipsia, ketonuria, and finally death unless exogenous insulin is administered (Chappel and Chappel, 1983;Like and Rossini, 1984). The incidence of diabetes through 120 days of age is 60 -90% in most colonies and averaged 86% in a viral antibody-free NIH colony in Worcester, Massachusetts (Crisa et al., 1992). The diabetes exhibited by BB rats is not attributed to a single dominant or recessive gene, but the etiology seems to include a genetic component (Chappel and Chappel, 1983).

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Section: Abstract: Diabetes; Glomerular Basement Membrane Thickness;mentioning

confidence: 99%

Significant glomerular basement membrane thickening in hyperglycemic and normoglycemic diabetic‐prone BB Wistar rats

et al. 2004

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“…However, lymphocytic insulitis, beta cell destruction and diabetes are induced in DR animals infected with the parvovirus Kilham Rat Virus (KRV) [10]. DR rats housed in conventional (i. e. virus-containing) surroundings display a low incidence of spontaneous diabetes, which is greatly increased by treatments which perturb the immune system, e.g., polyinosinic-polycytidylic acid (poly I : C) injections [11,12], depletion of RT6.1 + T-cells [13], X-irradiation [14] and cyclophosphamide [15].…”

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confidence: 99%

Preservation of GLUT 2 expression in islet beta cells of Kilham Rat Virus (KRV) ? infected diabetes-resistant BB/Wor rats

Stubbs

Guberski

1994

Diabetologia

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Summary Loss of GLUT 2, the glucose transporter isoform of pancreatic beta cells, has been reported to accompany the onset and perhaps contribute to the pathogenesis, of insulin-dependent and non-insulindependent diabetes mellitus in BB/Wor and Zucker fatty rats. In this study we investigated the effect of Kilham Rat Virus infection on GLUT 2 expression in diabetes-resistant BB/Wor rats. Viral antibodyfree diabetes-resistant rats do not develop spontaneous diabetes, but inoculation with Kilham Rat Virus induces autoimmune beta-cell destruction and hyperglycaemia. Pancreas sections from normoglycaemic diabetes-resistant BB/Wor rats were obtained 5, 7 and 25 days after inoculation with Kilham Rat Virus and stained for GLUT 2 using a rabbit polyclonal antibody. At all time points, beta cells displayed GLUT 2 expression comparable to uninfected diabetes-resistant controls. Immunostained insulin content of the beta cells also remained unchanged. Sections were also examined from Kilham Rat Virus inoculated diabetes-resistant rats with lymphocytic insulitis or diabetes. GLUT 2 and insulin immunostaining were unchanged in non-diabetic rats with early insulitis. GLUT 2 beta-cell staining was variably reduced in diabetic rats with established insulitis and reduced beta-cell insulin immunostaining. Hence, the initial stages of Kilham Rat Virus-induced diabetes in diabetes-resistant rats are not accompanied by a significant reduction in GLUT 2 expression. These results suggest that the loss of GLUT 2 does not play a significant role in the aetiology of diabetes in the Kilham Rat Virus-infected diabetes-resistant BB/Wor rat. [Diabetologia (1994) animal models of insulin dependent diabetes mellitus (IDDM) and non-insulin dependent diabetes mellitus (NIDDM) [4][5][6][7]. The Zucker diabetic fatty (ZDF) rat displays obesity and insulin resistance. Only male rats develop diabetes with an associated loss of insulin response to glucose [4]. Obese male diabetic ZDF rats revealed decreased beta-cell GLUT 2 protein and mRNA at the onset of diabetes, compared to obese non-diabetic female and lean non-diabetic male Zucker rats [4,6]. Glucose-induced insulin release in obese diabetic ZDF rats was correlated with the level of beta-cell GLUT 2; glucose-induced insulin release by the isolated perfused pancreas was absent in rats with fewer than 60 % GLUT 2 positive beta cells. In contrast, arginine infusions elicited a strong insulin secretory response,

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“…Lymphoid cell infiltration into pancreatic islets (insulitis) is a well-recognized feature of Type i (insulindependent) diabetes mellitus both in humans [1] and in rodents with spontaneous diabetes [2,3]. The nonobese diabetic (NOD) mouse spontaneously develops an insulin-dependent diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…The present data support the concept that production of oxygen free radicals mediated by macrophages can damage islet beta cells, directly resulting in autoimmune Type i diabetes in NOD mice. [Diabetologia (1994) 37: 22-31] Key words NOD mice, insulitis, reactive oxygen intermediates, superoxide dismutase, peritoneal macrophages.Lymphoid cell infiltration into pancreatic islets (insulitis) is a well-recognized feature of Type i (insulindependent) diabetes mellitus both in humans [1] and in rodents with spontaneous diabetes [2,3]. The nonobese diabetic (NOD) mouse spontaneously develops an insulin-dependent diabetes.…”

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confidence: 99%

Reactive oxygen intermediates in autoimmune islet cell destruction of the NOD mouse induced by peritoneal exudate cells (rich in macrophages) but not T cells

et al. 1994

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SummaryThe non-obese diabetic (NOD) mouse spontaneously develops autoimmune Type i (insulindependent) diabetes mellitus. NOD mice exhibit massive infiltrates of T cells and macrophages into pancreatic islets (insulitis) prior to diabetes. The contribution of oxygen free radicals to the development of insulitis in NOD mice was examined by administration of its scavengers, such as superoxide dismutase and catalase. Bovine superoxide dismutase and catalase were each coupled to polyethylene glycol. The treatment with superoxide dismutase-polyethylene glycol reduced the number of islets with insulitis and increased the undamaged islet tissue, as compared with the control group. The treatment with catalase-polyethylene glycol showed a similar tendency which did not reach significance. Using a flow cytometric assay of the oxidation of 2', 7'-dichlorofluorescein, the content of reactive oxygen intermediates in islet cells in the culture system was measured and the effect of peritoneal exudate cells and T cells on their production examined. Peritoneal exudate cells, but not T cells, from NOD mice increased the content of reactive oxygen intermediates in islet cells of either the NOD mouse or the ILI mouse (MHC-identical to NOD); the addition of snperoxide dismutase to the culture medium suppressed this increase in NOD or ILI islet cells. The present data support the concept that production of oxygen free radicals mediated by macrophages can damage islet beta cells, directly resulting in autoimmune Type i diabetes in NOD mice. [Diabetologia (1994) 37: 22-31] Key words NOD mice, insulitis, reactive oxygen intermediates, superoxide dismutase, peritoneal macrophages.Lymphoid cell infiltration into pancreatic islets (insulitis) is a well-recognized feature of Type i (insulindependent) diabetes mellitus both in humans [1] and in rodents with spontaneous diabetes [2,3]. The nonobese diabetic (NOD) mouse spontaneously develops an insulin-dependent diabetes. NOD mice exhibit massive infiltrates of lymphoid cells and macrophages into pancreatic islets (insulitis) prior to complete betacell destruction, and insulitis appears as early as 5 weeks of age. Makino and co-workers [4] have shown

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Spontaneous Autoimmune Diabetes mellitus in the BioBreeding/Worcester Rat

Cited by 40 publications

References 31 publications

Significant glomerular basement membrane thickening in hyperglycemic and normoglycemic diabetic‐prone BB Wistar rats

Significant glomerular basement membrane thickening in hyperglycemic and normoglycemic diabetic‐prone BB Wistar rats

Preservation of GLUT 2 expression in islet beta cells of Kilham Rat Virus (KRV) ? infected diabetes-resistant BB/Wor rats

Reactive oxygen intermediates in autoimmune islet cell destruction of the NOD mouse induced by peritoneal exudate cells (rich in macrophages) but not T cells

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