Altered expression of diabetes in BB/Wor rats by exposure to viral pathogens

Thomas, V. A.; Woda, Bruce A.; Handler, E. S.; Greiner, D. L.; Mordes, John P.; Rossini, A A

doi:10.2337/diabetes.40.2.255

Cited by 37 publications

(27 citation statements)

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“…We have reported previously that poly I:C administration accelerates diabetes in BB rats [8,9], while the present report describes the inhibition of the diabetic process by poly I:C. These disparate data appear to be due to the different dosages of poly I:C. Other than the use of a 100-fold lower poly I:C dosage, all other treatment parameters, including drug lot, age at initiation of drug treatment, and the frequency and route of poly I:C administration were the same in this report as in our previous study [8]. Several possibilities may underlie the surprising dose-dependent effects that we have observed.…”

Section: Discussionmentioning

confidence: 96%

“…It has been reported previously that treatment of diabetes-prone BB rats with high-dose poly I:C (5 g/gm body weight) accelerates the development of diabetes [8,9]. We now demonstrate that the administration of 50 (poly-0.1) and 100 (poly-0.05)-fold lower poly-I:C-dosages increases the rate of survival from diabetes in BB rats; poly-0.05 also increased the mean age of diabetes onset.…”

Section: Discussionmentioning

confidence: 99%

“…Polyinosinic polycytidylic acid (poly I:C), an inducer of cytokines, increases suppressor T-cell activity and inhibits the development of diabetes in the NOD mouse [7]. Surprisingly, poly-I:C administration was recently demonstrated to accelerate the development of diabetes in diabetesprone BB rats and even induce diabetes in diabetesresistant BB rates [8][9][10]. These contrary effects of poly I:C administration in the different animal models of IDDM are not understood.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Low Dose Poly I:C Prevents Diabetes in the Diabetes Prone BB Rat

Sobel

Goyal

Ahvazi

et al. 1998

Journal of Autoimmunity

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Low Dose Poly I:C Prevents Diabetes in the Diabetes Prone BB Rat

Sobel

Goyal

Ahvazi

et al. 1998

Journal of Autoimmunity

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“…Spontaneous type 1 diabetes does not occur in viral Ab-free BBDR rats (12), but the disorder can be induced in about one-third of these animals by infection with the UMass strain of rat virus (RV-UMass, formerly designated Kilham's rat virus) (13,14). Induction of diabetes is not associated with infection of the islets of Langerhans (15) and the combination of RV-UMass infection plus injection of the immune activator poly(I:C) leads to insulitis and diabetes in nearly all treated animals (16).…”

mentioning

confidence: 99%

Infections That Induce Autoimmune Diabetes in BBDR Rats Modulate CD4+CD25+ T Cell Populations

Zipris

Hillebrands

Welsh

et al. 2003

The Journal of Immunology

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Viruses are believed to contribute to the pathogenesis of autoimmune type 1A diabetes in humans. This pathogenic process can be modeled in the BBDR rat, which develops pancreatic insulitis and type 1A-like diabetes after infection with Kilham’s rat virus (RV). The mechanism is unknown, but does not involve infection of the pancreatic islets. We first documented that RV infection of BBDR rats induces diabetes, whereas infection with its close homologue H-1 does not. Both viruses induced similar humoral and cellular immune responses in the host, but only RV also caused a decrease in splenic CD4+CD25+ T cells in both BBDR rats and normal WF rats. Surprisingly, RV infection increased CD4+CD25+ T cells in pancreatic lymph nodes of BBDR but not WF rats. This increase appeared to be due to the accumulation of nonproliferating CD4+CD25+ T cells. The results imply that the reduction in splenic CD4+CD25+ cells observed in RV-infected animals is virus specific, whereas the increase in pancreatic lymph node CD4+CD25+ cells is both virus and rat strain specific. The data suggest that RV but not H-1 infection alters T cell regulation in BBDR rats and permits the expression of autoimmune diabetes. More generally, the results suggest a mechanism that could link an underlying genetic predisposition to environmental perturbation and transform a “regulated predisposition” into autoimmune diabetes, namely, failure to maintain regulatory CD4+CD25+ T cell function.

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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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Altered expression of diabetes in BB/Wor rats by exposure to viral pathogens

Cited by 37 publications

References 0 publications

Low Dose Poly I:C Prevents Diabetes in the Diabetes Prone BB Rat

Low Dose Poly I:C Prevents Diabetes in the Diabetes Prone BB Rat

Infections That Induce Autoimmune Diabetes in BBDR Rats Modulate CD4+CD25+ T Cell Populations

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

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