miR-378b Regulates Insulin Sensitivity by Targeting Insulin Receptor and p110α in Alcohol-Induced Hepatic Steatosis
miR-378b Regulates Insulin Sensitivity by Targeting Insulin Receptor and p110α in Alcohol-Induced Hepatic Steatosis
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miR-378b 通过靶向胰岛素受体和 p110α 在酒精诱导的肝脂肪变性中调节胰岛素敏感性
DOI：
10.3389/fphar.2020.00717
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发表时间：
2020-05-20
影响因子：
5.6
通讯作者：
Li, Li
中科院分区：
文献类型：
--
作者：
Li, Yuan-yuan;Zhong, Yu-juan;Li, Li
胰岛素抵抗与酒精性肝病有关。先前的研究表明，microRNAs（miRNAs）在胰岛素的产生、分泌和功能中起着重要作用。miRNA能够抑制多个靶基因，这些靶基因反过来负调节各种生理和病理活动。然而，目前关于miRNAs在胰岛素抵抗中的生物学功能的信息是有限的。本研究的目的是阐明miR-378 b在酒精诱导的肝脏胰岛素抵抗中的作用及其机制。本研究观察到miR-378 b在国立酒精滥用和酒精中毒研究所（NIAAA）酒精小鼠模型以及乙醇诱导的L-02细胞中上调。此外，miR-378 b过表达损害了胰岛素信号通路，并且miR-378 b的抑制提高了体内和体外胰岛素敏感性。一项机制研究表明，IR和p110α是miR-378 b的直接靶点。总之，这些结果表明，miR-378 b通过靶向胰岛素受体（IR）以及p110α来控制胰岛素敏感性，并可能在胰岛素抵抗的发展中发挥抑制作用，从而为开发新的诊断和治疗方法提供了见解。
Insulin resistance has been implicated in alcoholic liver disease. A previous study has shown that microRNAs (miRNAs) play a major role in the production, secretion, and function of insulin. MiRNAs are capable of repressing multiple target genes that in turn negatively regulate various physiological and pathological activities. However, current information on the biological function of miRNAs in insulin resistance is limited. The goal of the present study was to elucidate the role of miR-378b in alcohol-induced hepatic insulin resistance and its underlying mechanism. This study has observed that miR-378b is up-regulated in National Institute on Alcohol Abuse and Alcoholism (NIAAA) alcoholic mouse models as well as in ethanol-induced L-02 cells in vitro. Furthermore, miR-378b overexpression impaired the insulin signaling pathway, and inhibition of miR-378b improved insulin sensitivity in vivo and in vitro. A mechanistic study revealed that IR and p110α are direct targets of miR-378b. Together, these results suggest that miR-378b controls insulin sensitivity by targeting the insulin receptor (IR) as well as p110α and possibly play an inhibitory role in the development of insulin resistance, thereby providing insights into the development of novel diagnostic and treatment methods.