The Spontaneously Diabetic Torii (SDT) fatty rat, established by introducing the fa allele of the Zucker fatty rat into the SDT

We overviewed the pathophysiological features of diabetes and its complications in obese type 2 diabetic rat models: Otsuka Long-Evans Tokushima fatty (OLETF) rat, Wistar fatty rat, Zucker diabetic fatty (ZDF) rat and Spontaneously diabetic Torii (SDT) fatty rat. Pancreatic changes with progression of diabetes were classified into early changes, such as islet hypertrophy and degranulation of β cells, and degenerative changes, such as islet atrophy and fibrosis of islet with infiltration of inflammatory cells. Renal lesions in tubuli and glomeruli were observed, and nodular lesions in glomeruli were notable changes in OLETF and SDT fatty rats. Among retinal changes, folding and thickening were interesting findings in SDT fatty rats. A decrease of motor nerve conduction velocity with progression of diabetes was presented in obese diabetic rats. Other diabetic complications, osteoporosis and sexual dysfunction, were also observed. Observation of bone metabolic abnormalities, including decrease of osteogenesis and bone mineral density, and sexual dysfunction, including hypotestosteronemia and erectile dysfunction, in obese type 2 diabetic rats have been reported.

These findings indicate that ocular complications of SDT rats are caused by hyperglycaemia. The features of SDT rats indicate their usefulness for the future study of diabetic retinopathy.

Obesity, hyperglycemia, hyperlipidemia, and diabetes-associated complications appear at younger ages (6-8 weeks) in the male Spontaneously Diabetic Torii-Lepr fa (SDTfa/fa) rat than in the male original SDT (SDT-+/+) rat. However, the incidence and progression of diabetes mellitus and diabetic complications in the female SDT-fa/fa rat have not been reported in detail. In the present study, the pathophysiological features of the female SDT-fa/ fa rat were examined, and compared with those of the female SDT-+/+ rat. Female SDT-fa/ fa rats showed hyperphagia, obesity, hyperglycemia, and hyperlipidemia from 5 or 6 weeks of age, and hyperinsulinemia was observed from 5 to 12 weeks. Pathological changes pancreatic islets were observed from 8 weeks. Renal function parameters, such as urine volume and urinary protein, increased from 16 weeks, and pathological findings in the renal tubule, and cataracts were also observed from 16 weeks. Increases of visceral and subcutaneous fats were obvious during the observation period. In pair-feeding with SDT-+/+ rats, SDT-fa/fa rats showed improved hyperglycemia and hypertriglycemia, but hypercholesterolemia was not entirely improved during the study period. Female SDT-fa/fa rats showed diabetes mellitus and diabetes-associated complications at young ages, and fat accumulation was remarkable. Suppression of hyperphagia in SDT-fa/fa rats was effective at improving hyperglycemia and hypertriglycemia. In conclusion, the female SDT-fa/fa rat has the potential to become an important animal model of type 2 diabetes mellitus with obesity, especially for women, for which few models currently exist.

The spontaneously diabetic Torii (SDT) rat has recently been established as an animal model of non-obese type 2 diabetes, in which ocular

No abstract

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.

Spontaneously Diabetic Torii (SDT) rat shows severe ocular complications such as tractional retinal detachment. In the present study, effect of protein kinase C beta (PKCβ) inhibitor JTT-010 was evaluated to clarify the involvement of PKCβ in complications of SDT rat. SDT rats were administered JTT-010 (10 or 50 mg/kg/day) for 48 weeks. SDT rats showed delayed oscillatory potentials in electroretinogram. Delayed motor nerve conduction velocity, decreased coefficients of variation of R-R intervals in electrocardiogram and thermal hypoalgesia were also observed. These functional disorders were prevented by administration of JTT-010. Abnormal retinal vascular was formed and the optic disc was protruded in SDT rat; however, JTT-010 did not prevent these hyperglycaemia-induced retinal abnormalities. These findings indicate that PKCβ is intimately involved in diabetic complications; however, it seems that other factor(s) are primary contributors to histopathological abnormalities in retina. Therefore, PKCβ inhibitors require concurrent administration of antihyperglycaemic drugs to achieve maximum effect on diabetic complications.