Male ZDF rats were obtained from Charles River Laboratories at approximately 7 weeks of age. Rats were maintained ad lib on Purina #5008 diet, delivering approximately 17% of calories from fat. Animals with fasting glucose between 150–350 mg/dL were randomized based on glucose and body weight. Test articles were prepared in 0.5% (w/v) methylcellulose + 0.2% (w/v) Tween 80 and given by oral gavage twice daily. Rats (10/group, 6 treatment groups) were administered KDT501 (100, 150, or 200 mg/kg), metformin (200 mg/kg), pioglitazone (30 mg/kg) or vehicle control for up to 32 days. Body weights and food intake were determined weekly.
Blood was collected via tail bleed and whole blood glucose was measured on days 1, 8, 15 and 29. Blood was collected in 5 animals on days 15 and 29 for determination of glucose, insulin, lipids, hematocrit, and HbA1c. Animals were fasted overnight and OGTT was conducted on days 31 and 32 for determination of glucose and insulin levels. A second ZDF rat study was conducted and the resulting data on total cholesterol are presented.
Blood was collected via tail bleed and whole blood glucose was measured on days 1, 8, 15 and 29. Blood was collected in 5 animals on days 15 and 29 for determination of glucose, insulin, lipids, hematocrit, and HbA1c. Animals were fasted overnight and OGTT was conducted on days 31 and 32 for determination of glucose and insulin levels. A second ZDF rat study was conducted and the resulting data on total cholesterol are presented.