Development of β-Cells in the Native Pancreas After Pancreas Allo-Transplantation in the Spontaneously Diabetic Torii Rat

Shimada, Kazunori; Ito, Toshinori; Tanemura, Masahiro; Komoda, Hiroshi; Fumimoto, Yuichi; Kikuchi, Kôichi; Nishida, Toshirou; Kaneto, Hideaki; Sawa, Yoshiki

doi:10.1016/j.jss.2007.03.030

Cited by 6 publications

(3 citation statements)

References 42 publications

(42 reference statements)

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“…In SDT rats, it is suggested that the elimination of glucose toxicity following pancreas allotransplantation may induce the pancreatic expression of pancreatic and duodenal homeobox 1 (PDX-1), a homeodomain transcription factor, inhibiting the destruction of pancreatic islets and promoting the regeneration of pancreatic islets and β -cells [23, 24]. …”

Section: Phenotype and Clinical Characteristicsmentioning

confidence: 99%

The Spontaneously Diabetic Torii Rat: An Animal Model of Nonobese Type 2 Diabetes with Severe Diabetic Complications

Sasase

Ohta

Masuyama

et al. 2013

Journal of Diabetes Research

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The Spontaneously Diabetic Torii (SDT) rat is an inbred strain of Sprague-Dawley rat and recently is established as a nonobese model of type 2 diabetes (T2D). Male SDT rats show high plasma glucose levels (over 700 mg/dL) by 20 weeks. Male SDT rats show pancreatic islet histopathology, including hemorrhage in pancreatic islets and inflammatory cell infiltration with fibroblasts. Prior to the onset of diabetes, glucose intolerance with hypoinsulinemia is also observed. As a result of chronic severe hyperglycemia, the SDT rats develop profound complications. In eyes, retinopathy, cataract, and neovascular glaucoma are observed. Proliferative retinopathy, especially, resulting from retinal neovascular vessels is a unique characteristic of this model. In kidney, mesangial proliferation and nodular lesion are observed. Both peripheral neuropathy such as decreased nerve conduction velocity and thermal hypoalgesia and autonomic neuropathy such as diabetic diarrhea and voiding dysfunction have been reported. Osteoporosis is another complication characterized in SDT rat. Decreased bone density and low-turnover bone lesions are observed. Taking advantage of these features, SDT rat has been used for evaluating antidiabetic drugs and drugs/gene therapy for diabetic complications. In conclusion, the SDT rat is potentially a useful T2D model for studies on pathogenesis and treatment of diabetic complications in humans.

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Section: Phenotype and Clinical Characteristicsmentioning

confidence: 99%

The Spontaneously Diabetic Torii Rat: An Animal Model of Nonobese Type 2 Diabetes with Severe Diabetic Complications

Sasase

Ohta

Masuyama

et al. 2013

Journal of Diabetes Research

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“…In addition, it has been suggested that reactive oxygen species overproduction leads to manifestations of oxidative stress and apoptosis in ␤-cells in transgenic mouse models (6,7). Recently, Shimada et al (35,36) reported that allogeneic pancreas transplantation under immunosuppression can improve diabetes in SDT rats and the regeneration of ␤-cells in the native SDT pancreas. In these reports, they suggested that the amelioration of glucose toxicity improved the regeneration of the ␤-cells.…”

Section: Discussionmentioning

confidence: 99%

Identification of a major locus for islet inflammation and fibrosis in the spontaneously diabetic Torii rat

Fuse

Yokoi

Shinohara³

et al. 2008

Physiological Genomics

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of inflammation and fibrosis in the pancreatic islets in diabetes is largely unknown. Spontaneously diabetic Torii (SDT) rats exhibit inflammation and fibrosis in and around the islets during the development of the disease. We investigated genetic factors for diabetes, islet inflammation, and fibrosis in the SDT rat. We produced F1 and F2 rats by intercross between SDT and F344 rats, examined the onset of diabetes, glucose tolerance, and histology of the pancreas, and performed genetic analysis of these traits. We then established a congenic strain carrying the SDT allele at the strongest diabetogenic locus on the F344 genetic background and characterized glucose tolerance and histology of the pancreas. F1 rats showed glucose intolerance and inflammatory changes mainly in the islets. Genetic analysis of diabetes identified a major locus on chromosome 3, designated Dmsdt1, at which a dominantly acting SDT allele was involved. Quantitative trait locus (QTL) analysis of glucose tolerance revealed, in addition to Dmsdt1 [logarithm of odds (LOD) 5.3 near D3Mit12], three other loci, designated Dmsdt2 (LOD 4.2 at D8Rat46), Dmsdt3 (LOD 3.8 near D13Arb5), and Dmsdt4 (LOD 5.8 at D14Arb18). Analysis of a congenic strain for Dmsdt1 indicates that the dominantly acting SDT allele induces islet inflammation and fibrosis. Thus we have found a major locus on chromosome 3 for islet inflammation and fibrosis in the SDT rat. Identification of the genes responsible should provide insight into the pathogenesis of diabetes. congenic analysis; diabetes; genetic factor; glucose tolerance; quantitative trait locus DIABETES MELLITUS IS a multifactorial disease involving interaction of genetic and environmental factors. Spontaneous animal models of diabetes are widely used in research and have provided valuable information on the nature of the disease. Inflammation and fibrosis in pancreatic islets have been described in human type 2 diabetes (4) and in spontaneous animal models of type 2 diabetes, including the Goto-Kakizaki (GK) rat (12), the Zucker diabetic fatty rat (33), and the Otsuka Long-Evans Tokushima fatty (OLETF) rat (16). A role of inflammation and fibrosis in the pathogenesis of type 2 diabetes has been suggested (17), but the mechanism and genetic factors remain to be elucidated. Genetic, pathophysiological, and histological analyses using animal models should provide useful information for understanding the molecular mechanism of the inflammatory process in the development of the disease.The spontaneously diabetic Torii (SDT) rat was established from an outbred colony of Sprague-Dawley rats in 1997 as a nonobese diabetic animal model (37,38). Male SDT rats develop diabetes at 15 wk of age or later and show 100% incidence of diabetes by 40 wk of age. Pathological changes including microvascular congestion and hemorrhage in pancreatic islets appear from ϳ8 wk of age and are followed by inflammation and fibrosis in and around the islets. These pathological changes in the pancreas of SDT rats differ from those of typical autoi...

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“…Although the reason for this loss is unclear, possible contributory factors are exhaustion of surviving beta-cells by overwork and impaired proliferation (regeneration) of beta cells. In contrast, Simada et al [15,16] and Wiao et al [17,18] performed syngeneic or allogeneic pancreas transplantation to diabetic SDT rats. Interestingly, pancreas transplantation to diabetic SDT rats was beneficial in preventing glucose toxicity, and induced pancreatic duodenal homeobox-1 expression close to ductal structures in the recipient native pancreas.…”

Section: Pancreatic Isletsmentioning

confidence: 99%

Characteristics of Diabetes in the SDT Rat

Masuyama¹

2011

TODIAJ

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The Spontaneously Diabetic Torii (SDT) rat is a useful animal model of type 2 diabetes mellitus without obesity. The diabetes in this model manifests as severe hyperglycemia and hypoinsulinemia. However, insulin treatment is not required for survival despite marked hyperglycemia. Pancreatic islets display unique pathologic changes such as hemorrhage and fibrosis before the onset of hyperglycemia as well as marked atrophy. Islet injury is associated with macrophage infiltration of the islets and excess production of nitric oxide. Impaired glucose tolerance results from impaired insulin secretion following by decrease in beta cell mass and glucose-stimulated insulin release from beta cells. Beta cells in these animals have low insulin-secreting capacity in response to glucose stimulation, but retain normal responses to sulfonylurea and incretin. Although insulin resistance is less presented by body composition without obesity, the SDT rat has the potential contributions of hepatic insulin resistance and low energy expenditure to the development of diabetes. This article provides an overview of the pathologic features of pancreatic islets such as beta cell function and possible insulin resistance in SDT rats.

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Development of β-Cells in the Native Pancreas After Pancreas Allo-Transplantation in the Spontaneously Diabetic Torii Rat

Cited by 6 publications

References 42 publications

The Spontaneously Diabetic Torii Rat: An Animal Model of Nonobese Type 2 Diabetes with Severe Diabetic Complications

The Spontaneously Diabetic Torii Rat: An Animal Model of Nonobese Type 2 Diabetes with Severe Diabetic Complications

Identification of a major locus for islet inflammation and fibrosis in the spontaneously diabetic Torii rat

Characteristics of Diabetes in the SDT Rat

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