miR-320 mediates diabetes amelioration after duodenal-jejunal bypass via targeting adipoR1
miR-320 mediates diabetes amelioration after duodenal-jejunal bypass via targeting adipoR1
复制标题
miR-320通过靶向adipoR1介导十二指肠空肠旁路术后糖尿病的改善
DOI：
10.1016/j.soard.2018.03.007
复制
发表时间：
2018-07-01
影响因子：
3.1
通讯作者：
Hu Sanyuan
中科院分区：
文献类型：
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作者：
Guo Wei;Shao Yi;Hu Sanyuan
背景：十二指肠空肠旁路手术（DJB）可以显著改善2型糖尿病（T2D）。越来越多的证据表明，肝脂联素信号缺乏是糖异生疾病的一个因素，一些microrna （mirna）调节脂联素受体（AdipoR1, AdipoR2）。我们研究了DJB对肝脏糖异生、脂质代谢和炎症的影响，以及miRNA-320 （adipor1靶向miRNA）对DJB诱导的T2D改善的影响。目的：探讨mirna在DJB中以AdipoRl为靶点调控脂联素信号通路中的重要作用及其机制。单位：中国大学附属医院。方法：我们研究了大鼠DJB模型中肝脂联素信号的变化和肝脏mirna的变化。我们研究了miR-320对水牛大鼠肝细胞系AdipoR1信号传导的影响，并对注射了编码miR-320模拟物的慢病毒的DJB大鼠的肝组织和糖耐量试验进行了分析。结果：转染miR-320模拟物可降低AdipoR1蛋白水平并抑制下游脂联素信号传导；转染miR-320抑制剂会产生相反的效果。荧光素酶测定证实miR-320结合到AdipoR1的3'-非翻译区。在DJB大鼠中，miR-320表达的整体上调显示糖异生、脂质代谢受损，炎症标志物的表达相对较高。结论：miR-320调节adipor1介导的DJB中T2D的改善，应作为T2D治疗的潜在靶点进行探索。(C) 2018年由爱思唯尔公司代表美国代谢和减肥外科学会出版。
Background: Duodenal jejunal bypass (DJB) surgery can improve type 2 diabetes (T2D) dramatically. Accumulating evidence implicates deficiency of hepatic adiponectin signaling as a contributor to gluconeogenesis disorders, and some microRNAs (miRNAs) regulate adiponectin receptors (AdipoR1, AdipoR2). We investigated the effects of DJB on hepatic gluconeogenesis, lipid metabolism, and inflammation as well as the effects of miRNA-320 (AdipoR1-targeting miRNA) on DJB-induced T2D amelioration.Objectives: To investigate the essential role of miRNAs in regulation of adiponectin signaling by targeting AdipoRl in DJB and the underlying mechanisms.Setting: University Hospital, China.Methods: We studied hepatic adiponectin signaling changes and hepatic miRNAs involved in a rat model of DJB. We investigated the effects of miR-320 on AdipoR1 signaling in buffalo rat liver cell lines, Liver tissues and glucose tolerance tests were analyzed in DJB rats injected with lentivirus encoding a miR-320 mimic.Results: Transfection with a miR-320 mimic reduced AdipoR1 protein levels and inhibited downstream adiponectin signaling; transfection with a miR-320 inhibitor elicited the opposite effects. A luciferase assay confirmed that miR-320 binds to the 3'-untranslated regions of AdipoR1. Global upregulation of miR-320 expression in DJB rats showed impaired gluconeogenesis, lipid metabolism, and relatively higher expression of inflammation markers.Conclusion: miR-320 regulates the adipoR1-mediated amelioration of T2D in DJB and should be explored as a potential target for T2D treatment. (C) 2018 Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery.