Mechanism study of rosiglitazone in the treatment of type 2 KKay diabetic mice

Objective: To investigate rosiglitazone's mechanism in treating type 2 diabetes mellitus (T2DM) in KKay mice via urinary metabonomics. Methods: KKay mice were chosen as the model animals and given with rosiglitazone at a dose of 2 mg ·kg-1 by intragastric administration consecutively for 8 weeks, and C57BL/6J mice were used as normal controls. Urine samples were collected after the treatment, and the metabolic profiles of the urine samples were obtained with ultra performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC/TOF-MS). Then the mechanism underlying rosiglitazone in the treatment of T2DM was investigated from the perspective of global metabolic behaviors. Results: Urinary metabonomic study showed that tricarboxylic acid (TCA) cycle was diminished in the KKay mice, and glycolysis was enhanced as a metabolic compensation. Rosiglitazone treatment inhibited the acceleration of glycolysis and improved TCA cycle. Conclusion: Urine metabonomics analysis revealed the changes of metabolites traits during rosiglitazone treatment, thus providing a supplementary evaluation method for rosiglitazone in the treatment of type II diabetes.