Animal Models

The ZDF rats and the ZLC (Zucker lean control) rats were purchased from the Laboratory Animal Center of Vital River [Beijing, China; license number, SYXK (Yue) 2011 0074]. The ZDF rats exhibit a propensity for the development of T2DM after the administration of a high-fat diet purina#5008 and ZLC rats were used as the non-diabetic controls (9). Seven ZLC rats and 14 Male ZDF rats, at 8 weeks of age, were treated with high-fat diet purina#5008 for 4 weeks to induce diabetes. At 12 weeks of age, diabetic rats, as confirmed by random blood glucose level ≥300 mg/dl (16.7 mmol/L), were then randomly assigned to the diabetic control group (ZDF, n = 6) or the treatment group (ZDF+DA, n = 8). High-fat diet purina#5008 was provided from 8 weeks of age to the end of the experiment. At the beginning of the 13th week, rats in the ZDF+DA group were medicated with Dapagliflozin (1.0 mg/kg, once a day) via gavage. Rats in the ZDF group, treated with a vehicle via gavage, were used as the diabetic control and rats in the ZLC group were used as the negative control. At 21 weeks of age, the rats were anesthetized and sacrificed.