دورية أكاديمية
Exendin-4 Alleviates High Glucose-Induced Rat Mesangial Cell Dysfunction through the AMPK Pathway
| العنوان: | Exendin-4 Alleviates High Glucose-Induced Rat Mesangial Cell Dysfunction through the AMPK Pathway |
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| المؤلفون: | Wen-Wei Xu, Mei-Ping Guan, Zong-Ji Zheng, Fang Gao, Yan-Mei Zeng, Yan Qin, Yao-Ming Xue |
| المصدر: | Cellular Physiology and Biochemistry, Vol 33, Iss 2, Pp 423-432 (2014) |
| بيانات النشر: | Cell Physiol Biochem Press GmbH & Co KG, 2014. |
| سنة النشر: | 2014 |
| المجموعة: | LCC:Physiology LCC:Biochemistry |
| مصطلحات موضوعية: | Cell proliferation, Fibronectin, ERK, mTOR, MMP-2, TIMP-2, AMPK, Physiology, QP1-981, Biochemistry, QD415-436 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1015-8987 1421-9778 |
| Relation: | http://www.karger.com/Article/FullText/358623; https://doaj.org/toc/1015-8987; https://doaj.org/toc/1421-9778 |
| DOI: | 10.1159/000358623 |
| URL الوصول: | https://doaj.org/article/a97de62dba594c52a30f4a39d255c059 |
| رقم الأكسشن: | edsdoj.97de62dba594c52a30f4a39d255c059 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 10158987 14219778 |
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| DOI: | 10.1159/000358623 |