Dynamic Metabolic Profiling of Urine From Type 2 Diabetic KK-Ay Mice Treated with Repaglinide by GC-MS

Abstract

Repaglinide is a short-acting insulin secretagogue, commonly used for the treatment of type 2 diabetes. In this paper, metabolomics were first applied to research of dynamic urine metabolic profiling and biomarkers of type 2 diabetic KK-A^y mice treated with repaglinide based on GC-MS. Twenty diabetic KK-A^y mice were randomly assigned to four groups and fed with repaglinide for 6, 9, 12, and 14 weeks, respectively. Five C57BL/6 J mice were used as the healthy control group and fed with water as contrast. The PCA scores plot of the identified 41 metabolites showed that as treating time went on, the diabetic groups got closer to the healthy group. Furthermore, five marker metabolites, d-Glucose, d-Galactose, 1,5-Anhydro-d-glucitol, myo-inositol and tartaric acid were screened out, which have similar change footprints of the whole metabolic profiles. The results demonstrated that repaglinide not only regulates the sugars and polyalcohol but also the organic acid in the organism. This work has illustrated the potential of metabolomics to disease diagnosis, pharmacology, and pharmacodynamics research.

Keywords:

• KK-A^y mice
• Metabolomics
• Principal component analysis (pca)
• Repaglinide
• Type 2 diabetes mellitus

Acknowledgments

This work was supported financially by National Nature Foundation Committee of China (No.21105129), Special Fundation of China Postdoctoral Science (No. 200902481), Central South University Science Development Foundation (No. 10SDF22), the Fundamental Research Funds for the Central Universities (2010QZZD010 and 2011QNZT053), and the Program of the “Eleventh Five-year Plan” for “New Drug Research and Development” (2009ZX09303-008).

Notes

^a Retention time;.

^b Cannotbe identified by NIST05;.

^c No target product was detected;.

^d Identified by standard substances.