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Spontaneously Diabetic Torii Lepr fa (SDT fatty) rat, established by introducing the fa allele of the Zucker fatty rat into SDT rat genome, is a new model of obese type 2 diabetes. Both male and female SDT fatty rats show overt obesity, and hyperglycemia and hyperlipidemia are observed at a young age as compared with SDT rats. With early incidence of diabetes mellitus, diabetic complications, such as nephropathy, retinopathy, and neuropathy, in SDT fatty rats were seen at younger ages compared to those in the SDT rats. In this paper, we overview pathophysiological features in SDT fatty rats and also describe new insights regarding the hematology, blood pressure, renal complications, and sexual dysfunction. The SDT fatty rats showed an increase of leukocytes, especially the monocyte count, prominent hypertension associated with salt drinking, end-stage renal disease with aging, and hypogonadism. Unlike other diabetic models, the characteristic of SDT fatty rat is to present an incidence of diabetes in females, hypertension, and retinopathy. SDT fatty rat is a useful model for analysis of various metabolic disorders and the evaluation of drugs related to metabolic disease.

Abstract:The Spontaneously Diabetic Torii-Lepr fa (SDT-fa/fa) rat, a new model of obese type 2 diabetes, shows obesity, hyperglycemia, and hyperlipidemia from 6 weeks of age. Diabetic complications such as nephropathy and cataract are observed with aging; however, blood pressure change with age has not previously been examined. In this study, blood pressure was periodically measured and the change was investigated. Blood pressure in male SDT-fa/fa rats was elevated at 8, 16, and 24 weeks of age, whereas the heart rate was not changed. In addition to hyperglycemia, hyperlipidemia, and proteinuria, hyperleptinemia and increased urine angiotensinogen were observed in SDT-fa/fa rats. Blood pressure and heart rate in the male original SDT (SDT-+/+) rat did not significantly change. In conclusion, the SDT-fa/fa rat is a promising model, showing significant hypertension with diabetes mellitus. Key words: blood pressure, diabetes, SDT-fa/fa rat (Received 8 February 2010 / Accepted 21 March 2010 Address corresponding: T. Ohta, Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan Cardiovascular diseases are major causes of death in persons with diabetes, and many factors, including hypertension, contribute to this high prevalence of cardiovascular disease. Hypertension, a common comorbid condition in dysmetabolic syndrome, often occurs in patients with type 2 diabetes, and vigorous control of blood pressure decreases the rate of cardiovascular events in such patients. Control of high blood pressure represents the most important intervention for such patients, limiting cardiovascular events more effectively than tight glycemic control [1,2,15]. Moreover, metabolic syndrome is defined worldwide as a lifestyle disease, and is described as a clustering of multiple metabolic abnormalities and cardiovascular risk factors, including hypertension, obesity, hyperlipidemia, and insulin resistance [3]. From these and other perspectives, it is an important to examine the relation between glycolipid abnormalities and blood pressure.The Spontaneously Diabetic Torii-Lepr fa (SDT-fa/fa) rat is a new model of obese type 2 diabetes, and was established by introducing the fa gene of the Zuckerfatty rat into the SDT rat genome [8]. SDT-fa/fa rats exhibit hyperphagia and obesity immediately after weaning, and diabetes and its complications are found at a younger age in SDT-fa/fa rats than in SDT-+/+ rats [4,9,10,12]. However, blood pressure in SDT-fa/fa rats has not yet been examined. In the present study, we periodically investigated the blood pressure of male -Note-

Salt plays an important role in the control of blood pressure in obesity and diabetes mellitus. In this study, we investigated physiological changes such as blood pressure and renal function in salt-loaded female Spontaneously Diabetic Torii-Lepr(fa) (SDT fatty) rats. SDT fatty rats were given 1% NaCl in drinking water for 14 weeks, from 4 to 18 weeks of age. Significant salt-sensitive hypertension was observed in the salt-loaded SDT fatty rats. Moreover, the salt-loaded rats showed a decrease of creatinine clearance and deterioration on pathological renal findings, including glomerulosclerosis and tubular and interstitial lesions. Female SDT fatty rat is a useful model for investigating the mechanisms of high salt sensitivity in obesity and diabetes mellitus.

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