A new spontaneously diabetic strain of the Sprague-Dawley rat was established in 1997 and named the SDT (Spontaneously Diabetic Torii) rat. In this research, we investigated the characteristics of the disease condition in the SDT rats. The time of onset of glucosuria was different between male and female SDT rats; glucosuria appeared at approximately 20 weeks of age in male rats and at approximately 45 weeks of age in female rats. A cumulative incidence of diabetes of 100% was noted by 40 weeks of age in male rats, while it was only 33.3% even by 65 weeks of age in female rats. The survival rate up to 65 weeks of age was 92.9% in male rats and 97.4% in female rats. Glucose intolerance was observed in male rats from 16 weeks of age. The clinical characteristics of the male SDT rats were (1) hyperglycemia and hypoinsulinemia (from 25 weeks of age); (2) long-term survival without insulin treatment; (3) hypertriglyceridemia (by 35 weeks of age); however, no obesity was noted in any of the male rats. The histopathological characteristics of the male rats with diabetes mellitus (DM) were (1) fibrosis of the pancreatic islets (by 25 weeks of age); (2) cataract (by 40 weeks of age); (3) tractional retinal detachment with fibrous proliferation (by 70 weeks of age) and (4) massive hemorrhaging in the anterior chamber (by 77 weeks of age). These clinical and histopathological characteristics of the disease in SDT rats resemble those of human Type 2 diabetes with insulin hyposecretion. In conclusion, SDT rat is considered to be a potentially useful model for studies of diabetic retinopathy encountered in humans.

In order to estimate the potential risk of chemicals including drug in patients with type 2 diabetes mellitus (T2DM), we investigated allyl alcohol induced liver injury using SD rats and Spontaneously Diabetic Torii-Lepr fa (SDT fatty) rats as a model for human T2DM. The diabetic state is one of the risk factors for chemically induced liver injury because of lower levels of glutathione for detoxification by conjugation with chemicals and environmental pollutants and their reactive metabolites. Allyl alcohol is metabolized to a highly reactive unsaturated aldehyde, acrolein, which is detoxified by conjugation with glutathione. Therefore, we used allyl alcohol as a model compound. Our investigations showed that SDT fatty rats appropriately mimic the diabetic state in humans. The profiles of glucose metabolism, hepatic function tests and glutathione synthesis in the SDT fatty rats were similar to those in patients with T2DM. Five-week oral dosing with allyl alcohol to the SDT fatty rats revealed that the allyl alcohol induced liver injury was markedly enhanced in the SDT fatty rats when compared with the SD rats and the difference was considered to be due to lower hepatic detoxification of acrolein, the reactive metabolite of allyl alcohol, by depleted hepatic glutathione synthesis. Taking all the results of the present study into consideration, the potential for allyl alcohol to induce liver injury is considered to be higher in diabetic patients than in healthy humans.