PA01.71. Determination of Anti-Diabetic Potential of DB 14201 in Streptozotocin induced Type I Diabetes Mellitus in Rats

PURPOSE: Study is part of an ongoing reverse pharmacology approach in new drug develpement for diabetes. It was designed to determine anti diabetic potential of DB 14201 in streptozotocininduced Type I Diabetic rats in a GLP compliant setting. METHOD: Male wistar rats of 8 10 weeks and weighing 180 230 gm were used. After acclimatization, streptozotocin was administered by intravenous bolus injection. Stabilization period of 14 days followed screening with Glucose Tolerance Test. 24 rats with fasting glucose > 130mg/dl during the GTT profile were considered as diabetic and randomized into 3 groups. 8 untreated wistar rats were considered as non diabetic controls. Group I, the Non diabetic control group received sterile deionized water in equivalent volumes to the treatment. Group II, Hyperglycemic vehicle control group, received Streptozotocin and sterile deionized water in equivalent volumes to the treatment dose. Group III, the Hyperglycemic rats receiving DB14201 250mg/kg/day, and Group IV, the Hyperglycemic rats receiving DB14201 500mg/kg/day, also received Streptozotocin. Observations comprised of mortality, general cage side and clinical observations, and weekly blood glucose estimation. Biochemical parameters estimated on day 1 and day 15 were Serum Insulin Levels, Serum Triglycerides, Total Cholesterol Levels, Serum Urea, Serum Creatinine, SGPT levels, SGOT levels, Hepatic glycogen content, Polyuria, Polydipsia, Polyphagia, Diarrhea and , Body weight. RESULT: After 14 days of continuous treatment with DB 14201 in 500mg/kg treatment group, the blood glucose levels decreased by 85.24% showing a significant (P<0.01) anti hyperglycemic potential of the test item with reference to the hyperglycemic control animals. While a decline in blood glucose levels of animals treated with 250mg/kg of the test item was observed, this was not found to be statistically significant. CONCLUSION: The study clearly demonstrates that DB14201 is able to effectively bring down blood sugar levels in hyperglycemic rats after 14 days continuous oral administration and this activity is seen best at a dose of 500mg/kg/day.