Metabonomic analysis of the therapeutic effect of exendin-4 for the treatment of tBHP-induced injury in mouse glomerulus mesangial cells

Abstract

Although previous studies have reported the protective effect of glucagon-like peptide-1 (GLP-1) in diabetes nephropathy, the molecular mechanism such as nephroprotection remains elusive. In this study, we explored the molecular mechanism of exendin-4 as an GLP-1 receptor agonist for the treatment of tert-butyl hydroperoxide (t-BHP)-induced injury in mouse glomerulus mesangial cells (SV40 MES 13 cells) via an NMR-based metabonomic analysis. We found that exendin-4 protected mesangial cells from t-BHP-mediated toxicity, decreased the percentage of t-BHP-treated cells undergoing apoptosis, and restored glucose consumption in the t-BHP-treated group. A supervised partial least-squares discriminant analysis (PLS-DA) revealed that the metabolic profiles could be distinguished between the control, t-BHP-treated, and exendin-4-pretreated groups. Our findings indicate that exendin-4 pretreatment can cause distinct changes in energy, glycerol phospholipid, and amino acid metabolism. Our study provides novel insight into the metabolic mechanism of exendin-4-mediated nephroprotective effects.

Keywords:

• Diabetic nephropathy
• energy metabolism
• GLP-1
• metabonomics

Acknowledgements

Authors thank the staffs at the High-Field NMR Research Center, Xiamen University for their assistance.

Disclosure statement

No potential conflict of interest was reported by the authors to disclose.

Additional information

Funding

This work was supported by grants from the Joint Research Program of Fujian Provincial Health and Family Planning Commission and the Department of Education, Fujian Province [WKJ-FJ-12], the Key Clinical Specialty Discipline Construction Programs of Fujian (2015-SLN-08), the Financial Department Special Funds of Fujian Province ([2015]1297), and the Key Clinical Specialties Construction Program of Fujian Province ([2015]593).