Diabetes-associated complications in Spontaneously Diabetic Torii fatty rats.

The Spontaneously Diabetic Torii (SDT) fatty rat, established by introducing the fa allele of the Zucker fatty rat into the SDT rat genome, is a new model of obese type 2 diabetes. The SDT-fa/fa (SDT fatty) rat shows overt obesity, and hyperglycemia and hyperlipidemia are observed at a young age as compared with the SDT-+/+ (SDT normal) rat. However, the features of the diabetic complications in the SDT fatty rat have not been reported. In the present study, the incidence and the progression of diabetic complications in the SDT fatty rat were examined, and compared with those of the SDT normal rat. Renal function parameters, such as blood urea nitrogen, urine volume and urinary protein, increased from 4 weeks of age in the SDT fatty rat, and pathological findings in the renal tubule were observed from 8 weeks. Furthermore, cataract was observed in the SDT fatty rat from 8 weeks of age, and prolongation of peak latencies on electroretinograms was observed at 16 and 24 weeks of age. On the other hand, in the SDT normal rat, renal or ocular changes were observed from 24 weeks of age. With early incidence of diabetes mellitus, diabetes-associated complications in the SDT fatty rat were seen at younger ages than those in the SDT normal rat. In conclusion, the SDT fatty rat is expected to be a useful model for the analysis of diabetic complications and the evaluation of drugs related to metabolic diseases.

[1]  T. Sasase,et al.  Effect of insulin therapy on renal changes in spontaneously diabetic Torii rats. , 2007, Experimental animals.

[2]  T. Sasase,et al.  Preventive effects of glycaemic control on ocular complications of Spontaneously Diabetic Torii rat , 2006, Diabetes, obesity & metabolism.

[3]  Tomohiko Sasase,et al.  PKC : a target for treating diabetic complications , 2006 .

[4]  Z-W Yang,et al.  Glycogen accumulation in renal tubules, a key morphological change in the diabetic rat kidney , 2005, Acta Diabetologica.

[5]  M. Shinohara,et al.  A novel model of obesity-related diabetes: introgression of the Lepr(fa) allele of the Zucker fatty rat into nonobese Spontaneously Diabetic Torii (SDT) rats. , 2005, Experimental animals.

[6]  Y. Asano,et al.  [Revised criteria for the early diagnosis of diabetic nephropathy]. , 2005, Nihon Jinzo Gakkai shi.

[7]  M. Bleich,et al.  Nephroprotection in Zucker diabetic fatty rats by vasopeptidase inhibition is partly bradykinin B2 receptor dependent , 2004, British journal of pharmacology.

[8]  H. Tsujii,et al.  Genetic analysis for diabetes in a new rat model of nonobese type 2 diabetes, Spontaneously Diabetic Torii rat. , 2003, Biochemical and biophysical research communications.

[9]  M. Nagata,et al.  Podocyte Injury Promotes Progressive Nephropathy in Zucker Diabetic Fatty Rats , 2002, Laboratory Investigation.

[10]  T. Naka,et al.  Involvement of angiotensin II in progression of renal injury in rats with genetic non-insulin-dependent diabetes mellitus (Wistar fatty rats). , 2001, Japanese journal of pharmacology.

[11]  C. Lister,et al.  Rosiglitazone prevents the onset of hyperglycaemia and proteinuria in the Zucker diabetic fatty rat , 2000, Diabetes, obesity & metabolism.

[12]  K. Wakitani,et al.  Effects of peroxisome proliferator‐activated receptor‐α and ‐γ agonist, JTT‐501, on diabetic complications in Zucker diabetic fatty rats , 2000, British journal of pharmacology.

[13]  G. Brabant,et al.  Early events leading to renal injury in obese Zucker (fatty) rats with type II diabetes. , 2000, Kidney international.

[14]  K. Wakitani,et al.  Effects of peroxisome proliferator-activated receptor-alpha and -gamma agonist, JTT-501, on diabetic complications in Zucker diabetic fatty rats. , 2000, British journal of pharmacology.

[15]  A. Kakehashi,et al.  A New Spontaneously Diabetic Non-obese Torii Rat Strain With Severe Ocular Complications , 2000, International journal of experimental diabetes research.

[16]  T. Yoshimoto,et al.  Antihypertensive and vasculo- and renoprotective effects of pioglitazone in genetically obese diabetic rats. , 1997, The American journal of physiology.

[17]  H. Ikeda,et al.  Expression of ICAM-1 on glomeruli is associated with progression of diabetic nephropathy in a genetically obese diabetic rat, Wistar fatty. , 1996, Diabetes research and clinical practice.

[18]  S. Anderson,et al.  Evolution of metabolic and renal changes in the ZDF/Drt-fa rat model of type II diabetes. , 1996, Journal of the American Society of Nephrology : JASN.

[19]  T. Hostetter Diabetic Nephropathy: Metabolic versus hemodynamic considerations , 1992, Diabetes Care.

[20]  T. Deckert,et al.  Relationship Between Blood Pressure and Urinary Albumin Excretion in Development of Microalbuminuria , 1990, Diabetes.

[21]  D. West,et al.  Sexual Dimorphism of Hyperglycemia and Glucose Tolerance in Wistar Fatty Rats , 1989, Diabetes.

[22]  H. Ikeda,et al.  Pathogenesis of hyperglycemia in genetically obese-hyperglycemic rats, Wistar fatty: presence of hepatic insulin resistance. , 1989, Endocrinologia japonica.

[23]  Y. Hirata,et al.  The development of electroretinogram abnormalities and the possible role of polyol pathway activity in diabetic hyperglycemia and galactosemia. , 1988, Metabolism: clinical and experimental.

[24]  C. Mogensen Early glomerular hyperfiltration in insulin-dependent diabetics and late nephropathy. , 1986, Scandinavian journal of clinical and laboratory investigation.

[25]  H. Iwatsuka,et al.  A New Genetically Obese-Hyperglycemic Rat (Wistar Fatty) , 1981, Diabetes.