Diabetes-Associated Complications in Spontaneously Diabetic Torii Fatty Rats

Matsui, Kenichi; Ohta, Takeshi; Oda, Tomohiro; Sasase, Tomohiko; Ueda, Nobuhisa; Miyajima, Katsuhiro; Masuyama, Taku; Shinohara, Masami; Matsushita, Mutsuyoshi

doi:10.1538/expanim.57.111

Cited by 73 publications

(119 citation statements)

References 24 publications

(45 reference statements)

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“…Body weights and serum insulin levels of the SDT-+/+ rats decreased after 16 weeks of age (Table 1). Also, the increase of renal-related parameters such as BUN, urine volume, and urinary protein, was observed in SDT-fa/fa rats, similar to results reported in previous studies (Table 1) [4,10]. In addition to these changes, increases of serum leptin and urine angiotensinogen levels were shown by the SDT-fa/fa rats (Fig.…”

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Evaluation of Blood Pressure in Spontaneously Diabetic Torii-Leprfa Rats

et al. 2010

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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-

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confidence: 89%

“…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.…”

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Evaluation of Blood Pressure in Spontaneously Diabetic Torii-Leprfa Rats

et al. 2010

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“…This is in line with results from clinical studies demonstrating that in addition to hyperglycemia, other metabolic factors and blood pressure are involved in the manifestation and progression of retinopathy in humans. 4,54,55 In this regard, SHR/N-cp together with other non-STZ-based rat models [56][57][58][59][60][61][62][63][64] are useful tools to dissect the complexity of causative factors and disease mechanisms contributing to the varying spectrum of diabetic retinopathy. 55 Studies in these models have indeed revealed the contrasting impairment of the retina in the presence of cardiometabolic risk factors.…”

Section: Discussionmentioning

confidence: 99%

“…55 Studies in these models have indeed revealed the contrasting impairment of the retina in the presence of cardiometabolic risk factors. 62,63 Intervention during an early stage of the disease is particularly important to prevent manifestations of visual deterioration. 55,65 The latter aspect underscores the value of the SHR/N-cp model, which exhibits characteristics of the early phase of diabetic retinopathy.…”

Section: Discussionmentioning

confidence: 99%

Microangiopathy and visual deficits characterize the retinopathy of a spontaneously hypertensive rat model with type 2 diabetes and metabolic syndrome

et al. 2010

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Retinopathy has been increasing in prevalence as a consequence of type 2 diabetes and a cluster of coexisting risk factors characterized as the metabolic syndrome. However, the combined effects of these conditions on the retina are poorly understood. Therefore, we focused on the spontaneously hypertensive corpulent rat (SHR/N-cp), a model with type 2 diabetes, obesity and features of the metabolic syndrome to characterize retinal changes at a structural and functional level. SHR/N-cp males at 4 and 8 months of age were used in this study. Metabolic parameters and blood pressure were measured by standard methods. Morphology was investigated by histological techniques supplemented by nicotinamide adenine dinucleotide phosphate-diaphorase staining of whole mounts and fluorescein angiography to analyze the retinal vasculature. The in vivo function of the retina was examined by electroretinography (ERG). Obese SHR/N-cp rats were hypertensive and showed significant increases in body weight, serum levels of glucose, triglycerides, total cholesterol and urinary glucose excretion compared with lean controls (Po0.01 for each). Histology indicated an overall intact integrity of the retina and aspects of microangiopathy in obese SHR/N-cp rats. ERG revealed intact processing of light signals but significantly decreased amplitudes of b-waves for all (Po0.01) and of a-waves for some examined light intensities (Po0.05). Oscillatory potentials were significantly protracted (Po0.01), whereas amplitudes were not reduced. Microangiopathy and electroretinographic deficits combine to produce an early non-proliferative retinopathy phenotype in the obese SHR/N-cp rats. Thus, this model represents a valuable experimental tool to obtain further insights into the mechanisms of retinopathy in the context of obesity, type 2 diabetes and metabolic syndrome.

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“…Metabolic disorder in SDT fatty rats was obviously promoted as compared with SDT rats [104,105]. Serum glucose levels in SDT fatty rats of both sexes were elevated from 6 weeks, and lipid parameters such as serum triglyceride and total cholesterol levels in the rats were elevated from 4 weeks of age.…”

Section: Glucose Tolerance Insulin Sensitivity and Drug Treatmentmentioning

confidence: 92%