Exendin-4 Alleviates High Glucose-Induced Rat Mesangial Cell Dysfunction through the AMPK Pathway

Autor: Wen-Wei Xu, Mei-Ping Guan, Zong-Ji Zheng, Fang Gao, Yan-Mei Zeng, Yan Qin, Yao-Ming Xue
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: Cellular Physiology and Biochemistry, Vol 33, Iss 2, Pp 423-432 (2014)
Druh dokumentu: article
ISSN: 1015-8987
1421-9778
DOI: 10.1159/000358623
Popis: Background/Aims: Glucagon-like peptide-1 (GLP-1), which counteracts insulin resistance in humans with type 2 diabetes, has been shown to ameliorate diabetic nephropathy in experimental models. However, the mechanisms through which GLP-1 modulates renal function remained illdefined. The present study investigated the putative mechanisms underlying effects of exendin-4, a GLP-1 analog, on mesangial cell proliferation and fibronectin. Methods: Rat mesangial cells (MCs) were treated with exendin-4 under high glucose conditions. AMP-activated protein kinase (AMPK) inhibitors (compound C) and agonists (AICAR) were used to analyze the role of this kinase. Cell proliferation was measured using a MTT assay. Fibronectin expression and AMPK-signaling pathway activity were assessed using ELISA and Western blotting, respectively. The production of matrix metalloproteinase (MMP)-2 and tissue inhibitors of metalloproteinases (TIMP)-2 was evaluated using quantitative real-time RT-PCR. Results: Exendin-4 inhibited cell proliferation and fibronectin secretion in high glucose-induced MCs. It also caused phosphorylation of AMPK and subsequently increased the ratio of MMP-2 to TIMP-2, which resulted in the degradation of fibronectin. Exendin-4 reversed extracellular signal-regulated kinase (ERK) phosphorylation and enhanced expression of mammalian target of rapamycin (mTOR) in MCs. Moreover, the activation of the AMPK pathway by exendin-4 was induced by AICAR, which was inhibited by compound C. Conclusion: Exendin-4 exerts an inhibitory effect on cell proliferation and fibronectin secretion in rat MCs, partly through AMPK activation. These results may explain some of the beneficial effects of exendin-4 on the kidney.
Databáze: Directory of Open Access Journals
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