Comparison of Rosiglitazone and Metformin in Genetically Obese and Diabetic db/db Mice and Streptozotocin-Induced Diabetic Rat Models.
Kishor P. Patil1
and Pankaj Kothavade21Senior Scientist, Zydus Research Center, Ahmedabad - 382210, India.
2Pharmacology Lab 1, Department of Pharmaceutical Sciences, Institute of Chemical Technology, Matunga, Mumbai-400019, India.Corresponding Author E-mail: kpatil_23@yahoo.com
Abstract: Diabetes mellitus is a group of metabolic disorder which is characterized by high plasma glucose level and near or complete deficiency of insulin. It is a complex disorder, currently affecting 422 million people worldwide. This study was designed to compare the efficacy of rosiglitazone and metformin in db/db mice and STZ-induced rat models. Diabetes was induced by streptozotocin in rats. All the STZ-induced rats were orally administered with either rosiglitazone (10 mg/kg/day) or metformin (500 mg/kg/day) for 10 days. Groups of genetically diabetic db/db mice were orally administered with either rosiglitazone (5 mg/kg/day) or metformin (150 mg/kg/day) for 10 days. Fasting plasma glucose, serum insulin, body weight, cholesterol, triglyceride, serum glutamic pyruvic transaminase (SGPT) and serum glutamic-oxaloacetic transaminase (SGOT) were measured at 0, 5, 7 and 10 days after treatment using a Hitachi 7350 Auto analyzer. Serum insulin was measured p by enzyme-linked immunosorbent assay (ELISA). Our results indicated that fasting blood glucose levels in all the treatment groups were decreased substantially. A substantial decline in plasma glucose level was identified in rosiglitazone group (240.75 mg/dL ± 24.27, P<0.05 vs control- 541.65 mg/dL) as compared to metformin group (304.35 mg/dL ±33. 34, P<0.05) in db/db mice. A significant reduction in serum insulin was observed in rosiglitazone group (15.88 ng/mL ± 2.89, p<0.05 vs control- 32.65 ng/mL) and cholesterol level (52.35 ± 5. 48 mg/dL, p<0.05) compared with control (32.65 ng/mL ± 4.66 and 129.48 ± 15.82 mg/dL) in db/db mice. Moreover, significantly (p<0.05) decrease in plasma glucose (467.6 ± 56.90 mg/dL, p<0.05) and serum insulin (27.05 ± 7.56 ng/mL, p<0.05) level were observed in the metformin group compared with the diabetic control group (649.55 ± 80.26 mg/dL and 37.68 ± 4.66 ng/mL) into STZ-induced diabetic rats. Results suggest that, rosiglitazone is more efficacious than metformin on the lipid-lowering and plasma glucose profile in db/db mice. In contrast, metformin is more efficacious than rosiglitazone in STZ-induced diabetic rat model with respect to antihyperglycemic effect.
Keywords: Diabetic db/db Genetically Obese Mice; Mice Insulin Resistance; Metformin; Rosiglitazone; Streptozotocin-Induced Diabetes; Back to TOC