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肝 miR-215 靶向 Rictor 与大鼠肝胰岛素信号转导的调节。

Hepatic miR‑215 target Rictor and modulation of hepatic insulin signalling in rats.

机构信息

Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.

Department of Preventive Medicine, Jiangsu Health Vacation College, Nanjing, Jiangsu 210036, P.R. China.

出版信息

Mol Med Rep. 2019 May;19(5):3723-3731. doi: 10.3892/mmr.2019.10031. Epub 2019 Mar 14.

Abstract

Increasing evidence has suggested that hepatic lipid accumulation is associated with hepatic insulin resistance; however, the underlying mechanism is yet to be determined. It was demonstrated that the levels of microRNA‑215 (miR‑215) expression in the liver of rats fed a high‑fat diet were significantly increased compared with rats on a control diet. Additionally, it was revealed via luciferase assays and western blotting that miR‑215 targets rapamycin‑insensitive companion of mammalian target of rapamycin (Rictor), an important protein in the hepatic insulin signalling pathway. Following overexpression of miR‑215 in the H4IIE rat hepatocarcinoma cell line, it was reported that the intracellular insulin signalling pathway was inhibited; conversely, inhibition of miR‑215 expression induced this pathway. Furthermore, it was demonstrated via reverse transcription‑quantitative polymerase chain reaction analysis that free fatty acids promoted the expression of miR‑215. The present study provided a novel mechanistic insight into the association between nonalcoholic fatty liver and hepatic insulin resistance.

摘要

越来越多的证据表明,肝脏脂质积累与肝胰岛素抵抗有关;然而,其潜在机制尚待确定。研究表明,高脂肪饮食喂养的大鼠肝脏中 microRNA-215 (miR-215) 的表达水平明显高于对照饮食喂养的大鼠。此外,通过荧光素酶测定和 Western blot 分析显示,miR-215 靶向雷帕霉素不敏感的哺乳动物雷帕霉素靶蛋白(mTOR)伴侣 rapamycin-insensitive companion of mammalian target of rapamycin (Rictor),这是肝胰岛素信号通路中的一种重要蛋白。在 H4IIE 大鼠肝癌细胞系中转染 miR-215 后,据报道,细胞内胰岛素信号通路受到抑制;相反,抑制 miR-215 的表达则诱导该通路。此外,通过逆转录-定量聚合酶链反应分析表明,游离脂肪酸促进了 miR-215 的表达。本研究为非酒精性脂肪肝和肝胰岛素抵抗之间的关联提供了一种新的机制见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4144/6471735/0bdb8b082dd7/MMR-19-05-3723-g00.jpg

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