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Free Radic Res. 2018 May;52(5):544-555. doi: 10.1080/10715762.2018.1449948. Epub 2018 Mar 27.

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

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a Department of Endocrinology and Metabolism, Department of Geriatrics , Fujian Institute of Endocrinology, Fujian Medical University Union Hospital , Fuzhou , China.
b Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering , Xiamen University , Xiamen , China.
c Department of Pharmacology, College of Pharmacy , Fujian Medical University , Fuzhou , China.
d Exercise and Health Laboratory , Xiamen University of Technology , Xiamen , China.


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.


Diabetic nephropathy; GLP-1; energy metabolism; metabonomics

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