Liraglutide inhibits autophagy and apoptosis induced by high glucose through GLP-1R in renal tubular epithelial cells.
Liraglutide inhibits autophagy and apoptosis induced by high glucose through GLP-1R in renal tubular epithelial cells.
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利拉鲁肽通过GLP-1R抑制高糖诱导的肾小管上皮细胞自噬和凋亡
DOI：
10.3892/ijmm.2014.2052
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发表时间：
2015-03
影响因子：
5.4
通讯作者：
Ji Q
中科院分区：
文献类型：
--
作者：
Zhao X;Liu G;Shen H;Gao B;Li X;Fu J;Zhou J;Ji Q
肾小管萎缩和功能障碍是糖尿病肾病（DN）的一个关键过程。了解肾小管上皮细胞存活的机制对于预防与糖毒性相关的肾衰竭非常重要。自噬是参与蛋白质和细胞器降解的细胞途径。它与多种类型的细胞稳态和人类疾病有关。迄今为止，人们对高浓度葡萄糖与肾小管细胞自噬之间的关系知之甚少。在本研究中，我们通过几种补充测定研究了高葡萄糖诱导的肾小管上皮细胞毒性，包括细胞活力、细胞死亡测定和永生化人肾细胞系 HK-2 细胞超微结构的变化。在用高水平葡萄糖处理后，HK-2细胞的凋亡程度显着增加。此外，在糖尿病大鼠的体内实验中，高血糖对糖尿病大鼠的肾脏组织结构产生有害影响。肾病大鼠的 HK-2 细胞和肾小管上皮细胞长期暴露于高水平葡萄糖诱导的自噬。利拉鲁肽抑制了这些作用；然而，用胰高血糖素样肽 1 受体 (GLP-1R) 拮抗剂治疗可增强这些作用。我们的结果还表明，肾小管上皮细胞在体外暴露于高浓度葡萄糖会导致 GLP-1R 表达下调。利拉鲁肽逆转了这种作用，而 GLP-1R 拮抗剂则促进了这种作用，促进自噬，这表明利拉鲁肽在高葡萄糖存在下发挥肾脏保护作用，至少部分是通过抑制自噬并增加糖尿病大鼠 HK-2 细胞和肾脏中 GLP-1R 的表达。
Tubular atrophy and dysfunction is a critical process underlying diabetic nephropathy (DN). Understanding the mechanisms underlying renal tubular epithelial cell survival is important for the prevention of kidney failure associated with glucotoxicity. Autophagy is a cellular pathway involved in protein and organelle degradation. It is associated with many types of cellular homeostasis and human diseases. To date, little is known of the association between high concentrations of glucose and autophagy in renal tubular cells. In the present study, we investigated high glucose-induced toxicity in renal tubular epithelial cells by means of several complementary assays, including cell viability, cell death assays and changes in ultrastructure in an immortalized human kidney cell line, HK-2 cells. The extent of apoptosis was significantly increased in the HK-2 cells following treatment with high levels of glucose. In addition, in in vivo experiments using diabetic rats, high glucose exerted harmful effects on the tissue structure of the kidneys in the diabetic rats. Chronic exposure of the HK-2 cells and tubular epithelial cells of nephritic rats to high levels of glucose induced autophagy. Liraglutide inhibited these effects; however, treatment witht a glucagon-like peptide-1 receptor (GLP-1R) antagonist enhanced these effects. Our results also indicated that the exposure of the renal tubular epithelial cells to high glucose concentrations in vitro led to the downregulation of GLP-1R expression. Liraglutide reversed this effect, while the GLP-1R antagonist promoted it, promoting autophagy, suggesting that liraglutide exerts a renoprotective effect in the presence of high glucose, at least in part, by inhibiting autophagy and increasing GLP-1R expression in the HK-2 cells and kidneys of diabetic rats.
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影响因子：
8.2
作者：
Masini, M.;Bugliani, M.;Marchetti, P.
通讯作者：
Marchetti, P.
影响因子：
4.8
作者：
Bullock, BP;Heller, RS;Habener, JF
通讯作者：
Habener, JF
影响因子：
29
作者：
Ebato, Chie;Uchida, Toyoyoshi;Watada, Hirotaka
通讯作者：
Watada, Hirotaka
影响因子：
15.9
作者：
Koya, D;Jirousek, MR;King, GL
通讯作者：
King, GL
影响因子：
6.1
作者：
Kawakami, Takahisa;Inagi, Reiko;Nangaku, Masaomi
通讯作者：
Nangaku, Masaomi