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  • Title: Liraglutide promotes autophagy by regulating the AMPK/mTOR pathway in a rat remnant kidney model of chronic renal failure.
    Author: Xue L, Pan Z, Yin Q, Zhang P, Zhang J, Qi W.
    Journal: Int Urol Nephrol; 2019 Dec; 51(12):2305-2313. PubMed ID: 31531806.
    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.
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