Effect of Insulin Therapy on Renal Changes in Spontaneously Diabetic Torii Rats

The spontaneously diabetic Torii (SDT) rat has recently been established as an animal model of non-obese type 2 diabetes, in which ocular complications severe occur. However, the function and morphological features of the diabetic renal lesions in SDT rats have not been reported in detail. Therefore, we evaluated changes over time in renal lesions in SDT rats. In addition, SDT rats were treated with insulin to observe whether these renal complications are caused by hyperglycemia. Renal functional parameters and renal lesions were monitored in SDT rats from 8 to 68 weeks of age. Sprague-Dawley (SD) rats of similar age were used as control animals. In the insulin-treated group of SDT rats, insulin pellets were implanted at 24 weeks of age to compare the development of renal lesions. The SDT rats began to develop hyperglycemia at 20 weeks of age. In the histopathological examination of the kidney, glycogen deposition of the renal tubular epithelium and renal tubular dilation were observed from 24 weeks of age in the untreated SDT rats, and the changes in the renal tubules markedly progressed with aging. Moreover, thickening of the glomerular basement membrane was observed from 32 weeks of age. At 50 weeks of age, the glomeruli showed increase of mesangial matrix, with predominantly diffuse lesions showing by 68 weeks of age. The mesangial proliferation gradually progressed. In the SD rats, no renal lesions were present at 50 and 68 weeks of age. SDT rats with insulin treatment remained normoglycemic throughout observation and their renal functional parameters were normal. Glycemic control in SDT rats prevented the development of renal lesions. The features of SDT rats indicate their usefulness as an animal model for investigating diabetic nephropathy.