Pathology of the pancreas and other organs in the diabetic LEW.1AR1/Ztm- iddm rat, a new model of spontaneous insulin-dependent diabetes mellitus

Jörns, Anne; Kubat, Birgit; Tiedge, Markus; Wedekind, Dirk; Hedrich, Hans-Jürgen; Klöppel, Günter; Lenzen, Sigurd

doi:10.1007/s00428-003-0956-2

Cited by 34 publications

(25 citation statements)

References 21 publications

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“…Interestingly, another recently described rat strain that also exhibits spontaneous autoimmune diabetes, the LEW.1AR1/Ztm-iddm strain has the RT1 A a B/D u C u (RT1 r2 ) MHC haplotype (33,34). These observations further confirm the critical importance of the u allele of RT1 B/D and confirm that diabetes susceptibility is preserved in the presence of non-u class I alleles at either the A or C locus (35,36).…”

Section: Discussionsupporting

confidence: 71%

LEW.1WR1 Rats Develop Autoimmune Diabetes Spontaneously and in Response to Environmental Perturbation

et al. 2005

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We describe a new rat model of autoimmune diabetes that arose in a major histocompatibility complex congenic LEW rat. Spontaneous diabetes in LEW.1WR1 rats (RT1 u/u/a ) occurs with a cumulative frequency of ϳ2% at a median age of 59 days. The disease is characterized by hyperglycemia, glycosuria, ketonuria, and polyuria. Both sexes are affected, and islets of acutely diabetic rats are devoid of ␤-cells, whereas ␣-and ␦-cell populations are spared. The peripheral lymphoid phenotype is normal, including the fraction of ART2 ؉ regulatory T-cells. We tested the hypothesis that the expression of diabetes would be increased by immunological perturbation of innate or adaptive immunity. Treatment of young rats with depleting anti-ART2.1 monoclonal antibody increased the frequency of diabetes to 50%. Treatment with the toll-like receptor 3 ligand polyinosinic:polycytidylic acid increased the frequency of diabetes to 100%. All diabetic rats exhibited end-stage islets. The LEW.1WR1 rat is also susceptible to collagen-induced arthritis but is free of spontaneous thyroiditis. The LEW.1WR1 rat provides a new model for studying autoimmune diabetes and arthritis in an animal with a genetic predisposition to both disorders that can be amplified by environmental perturbation. Diabetes 54: 2727-2733, 2005

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Section: Discussionsupporting

confidence: 71%

LEW.1WR1 Rats Develop Autoimmune Diabetes Spontaneously and in Response to Environmental Perturbation

et al. 2005

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“…These activated inflammatory cells produce cytokines, such as IL-1β, IFNγ, and TNF-α, which cause progressive destruction of most β-cells via apoptosis, leading to an absolute deficiency of insulin [46]. Based on animal studies, it is assumed that decreased beta cell mass in DM1 is due to increased beta cell apoptosis [47]. Beta cells are also vulnerable to apoptosis when exposed to glucose concentrations of approximately 11 mmol/l (200 mg/dl) or higher through mechanisms that include β cell expression and the action of IL-1 [48].…”

Section: Discussionmentioning

confidence: 99%

Effect of Quercetin on the Endocrine Pancreas of the Experimentally Induced Diabetes in Male Albino Rats: A Histological and Immunohistochemical Study

Rifaai¹,

El‐Tahawy²,

Saber³

et al. 2012

J Diabetes Metab

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Background: Insulin dependent diabetes mellitus is a chronic metabolic disease. Many drugs used in its treatment which have a number of serious adverse effects. Natural agent as quercetin (QCT) has been suggested in the alternative medicine for treatment of diabetes mellitus. Aim of the work:To evaluate the effect of QCT on the histological changes which occur in the islet of Langerhans of the streptozotocin (STZ)-induced diabetic rats and the possible mechanisms through which QCT produces its protective effect. Materials and methods:Fourty five male albino rats were divided into 3 groups: Group I, control group; 15 rats received single intraperitoneal injection of citrate buffer saline. Group II, diabetic group; 15 rats received single intraperitoneal injection of STZ. Group III; QCT-treated group, 15 rats received daily intraperitoneal injections of QCT for 30 days prior to, and for 30 days after the single injection of STZ. Blood samples were taken for monitoring blood glucose levels. Pancreas was taken out and processed for light microscopic, immunocytochemical and morphometrical studies.Results: Blood glucose levels showed a significant increase in group II compared to the control, while a significant decrease was observed in groups III compared to group II (all p<0.05). In the hematoxylin-eosin stained sections, STZ administration caused marked degeneration of islet Beta cells with inflammatory cells infiltration. Using QCT; in group III, reversed most of the pancreatic morphological changes, and interestingly some islets noticed with connections to some pancreatic ducts. In chrome alum heamatoxylin stained sections, STZ administration caused a significant decrease in the number of bluish stained β cells compared to controls. While group III showed a significant increase in β cells number compared to group II (all p<0.05). Sections of animals injected with charcoal, showed many charcoal labeled macrophages in group II compared to group III, and controls. There was increased iNOS and caspase 3 immunoreactivity in islets cells of group II than in controls, and was decreased in group III. Conclusion:This study provides evidence that quercetin could exert a protective effect against β cell damage by its anti-inflammatory, anti-apoptotic, and antioxidant effects; and aids regeneration of β cells which might through stimulation of the ductal stem cells. However, further experimental studies are still needed for more details on quercetin as an adjuvant drug in management of diabetes mellitus. Journal of Diabetes and MetabolismCitation: Rifaai RA, El-Tahawy NF, Saber EA, Ahmed R (2012) Effect of Quercetin on the Endocrine Pancreas of the Experimentally Induced Diabetes in Male Albino Rats: A Histological and Immunohistochemical Study. J Diabetes Metab 3:182.

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“…Based on animal studies, it is assumed that decreased beta cell mass in type 1 diabetes is due to increased beta cell apoptosis [13,14]. It has been reported that some patients with long-standing type 1 diabetes have occasional beta cells scattered in the pancreas [3,8].…”

Section: Introductionmentioning

confidence: 99%

Sustained beta cell apoptosis in patients with long-standing type 1 diabetes: indirect evidence for islet regeneration?

Meier¹,

Bhushan²,

Butler³

et al. 2005

Diabetologia

456

383

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Aims/hypothesis: Type 1 diabetes is widely held to result from an irreversible loss of insulin-secreting beta cells. However, insulin secretion is detectable in some people with long-standing type 1 diabetes, indicating either a small population of surviving beta cells or continued renewal of beta cells subject to ongoing autoimmune destruction. The aim of the present study was to evaluate these possibilities. Materials and methods: Pancreatic sections from 42 individuals with type 1 diabetes and 14 non-diabetic individuals were evaluated for the presence of beta cells, beta cell apoptosis and replication, T lymphocytes and macrophages. The presence and extent of periductal fibrosis was also quantified. Results: Beta cells were identified in 88% of individuals with type 1 diabetes. The number of beta cells was unrelated to duration of disease (range 4-67 years) or age at death (range 14-77 years), but was higher (p<0.05) in individuals with lower mean blood glucose. Beta cell apoptosis was twice as frequent in type 1 diabetes as in control subjects (p<0.001), but beta cell replication was rare in both groups. The increased beta cell apoptosis in type 1 diabetes was accompanied by both increased macrophages and T lymphocytes and a marked increase in periductal fibrosis (p<0.001), implying chronic inflammation over many years, consistent with an ongoing supply of beta cells. Conclusions/interpretation: Most people with long-standing type 1 diabetes have beta cells that continue to be destroyed. The mechanisms underlying increased beta cell death may involve both ongoing autoimmunity and glucose toxicity. The presence of beta cells despite ongoing apoptosis implies, by definition, that concomitant new beta cell formation must be occurring, even after long-standing type 1 diabetes. We conclude that type 1 diabetes may be reversed by targeted inhibition of beta cell destruction.

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Pathology of the pancreas and other organs in the diabetic LEW.1AR1/Ztm- iddm rat, a new model of spontaneous insulin-dependent diabetes mellitus

Cited by 34 publications

References 21 publications

LEW.1WR1 Rats Develop Autoimmune Diabetes Spontaneously and in Response to Environmental Perturbation

LEW.1WR1 Rats Develop Autoimmune Diabetes Spontaneously and in Response to Environmental Perturbation

Effect of Quercetin on the Endocrine Pancreas of the Experimentally Induced Diabetes in Male Albino Rats: A Histological and Immunohistochemical Study

Sustained beta cell apoptosis in patients with long-standing type 1 diabetes: indirect evidence for islet regeneration?

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