Lingyu Xue1, Zhanglei Pan2, Qiao Yin2, Peng Zhang2, Jing Zhang2, Wenwen Qi2. 1. Department of Nephrology, The Second Affiliated Hospital of Shandong First Medical University, No. 706, Taishan Street, Taian, 271000, Shandong, China. lingyuxue1122@163.com. 2. Department of Nephrology, The Second Affiliated Hospital of Shandong First Medical University, No. 706, Taishan Street, Taian, 271000, Shandong, China.
Abstract
BACKGROUND: We aimed to determine whether the glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide (LRG) could ameliorate renal function through promoting autophagy via regulating the AMPK/mTOR pathway in a rat remnant kidney model of chronic renal failure. METHODS: Rats were divided into four groups (n = 10 per group) as follows: (1) sham, (2) nephrectomy (NPX), (3) LRG control (LRG control), and (4) LRG treatment (LRG). Except for rats in the sham group, all rats underwent 5/6 nephrectomy surgery to establish a remnant kidney model of chronic renal failure. In addition, rats in LRG group received LRG as a subcutaneous injection at a dose of 10 mg/kg (once daily) for 4 consecutive weeks, whereas rats in the LRG control group received treatment similar to that of rats in the LRG group, except saline was used instead of LRG. After 4 weeks of treatment, serum creatinine (Scr), blood urea nitrogen (BUN), and urinary albumin excretion were determined. Immunofluorescence assay, immunoprecipitation assay, and Western blot analysis were performed to evaluate the AMPK/mTOR pathway expression of proteins. RESULTS: Nephrectomized rats (including rats in the NPX, LRG control, and LRG groups) showed higher levels of the Scr, BUN, and urinary albumin excretion, as well as down-regulation of GLP-1R, LC3-II, and AMPK phosphorylation, and up-regulation of mTOR phosphorylation when compared with rats in the sham group. However, those changes were blocked by liraglutide. CONCLUSION: Liraglutide may promote autophagy through regulating the AMPK/mTOR pathway to exert renoprotective effects in a rat remnant kidney model of chronic renal failure.
BACKGROUND: We aimed to determine whether the glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide (LRG) could ameliorate renal function through promoting autophagy via regulating the AMPK/mTOR pathway in a rat remnant kidney model of chronic renal failure. METHODS:Rats were divided into four groups (n = 10 per group) as follows: (1) sham, (2) nephrectomy (NPX), (3) LRG control (LRG control), and (4) LRG treatment (LRG). Except for rats in the sham group, all rats underwent 5/6 nephrectomy surgery to establish a remnant kidney model of chronic renal failure. In addition, rats in LRG group received LRG as a subcutaneous injection at a dose of 10 mg/kg (once daily) for 4 consecutive weeks, whereas rats in the LRG control group received treatment similar to that of rats in the LRG group, except saline was used instead of LRG. After 4 weeks of treatment, serum creatinine (Scr), blood ureanitrogen (BUN), and urinary albumin excretion were determined. Immunofluorescence assay, immunoprecipitation assay, and Western blot analysis were performed to evaluate the AMPK/mTOR pathway expression of proteins. RESULTS: Nephrectomized rats (including rats in the NPX, LRG control, and LRG groups) showed higher levels of the Scr, BUN, and urinary albumin excretion, as well as down-regulation of GLP-1R, LC3-II, and AMPK phosphorylation, and up-regulation of mTOR phosphorylation when compared with rats in the sham group. However, those changes were blocked by liraglutide. CONCLUSION: Liraglutide may promote autophagy through regulating the AMPK/mTOR pathway to exert renoprotective effects in a rat remnant kidney model of chronic renal failure.
Authors: G Muscogiuri; A Cignarelli; F Giorgino; F Prodam; F Prodram; D Santi; G Tirabassi; G Balercia; R Modica; A Faggiano; A Colao Journal: J Endocrinol Invest Date: 2014-08-09 Impact factor: 4.256
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