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桑色素通过下调miR-29a在人肝癌细胞系HepG2中发挥抗糖尿病作用。

Morin Exerts Anti-Diabetic Effects in Human HepG2 Cells Via Down-Regulation of miR-29a.

作者信息

Razavi Toktam, Kouhsari Shideh Montasser, Abnous Khalil

机构信息

Department of Cellular and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.

Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Exp Clin Endocrinol Diabetes. 2019 Oct;127(9):615-622. doi: 10.1055/a-0650-4082. Epub 2018 Oct 8.

Abstract

is a complex metabolic disease around the world that is characterized by hyperglycemia resulting from impaired insulin secretion, insulin action, or both. MicroRNA-29a is an important regulator of insulin signaling and gluconeogenesis pathways through , and expressions which up regulates in Diabetes. Morin is a substantial bioflavonoid which has insulin mimetic effect, and interacting with nucleic acids and proteins. In this study HepG2 cells, were exposed to high glucose to induce diabetic condition. We have determined whether high glucose stimulation might promotes miR-29a expression level in HepG2 cells and subsequently evaluated the Morin treatment effects on this state. In HepG2 cells, high glucose increases miR-29a expression level and decreases its target genes, and expression, and increases associated downstream gene in gluconeogenic pathway, . Morin treatment down regulates miR-29a expression level and improves insulin signaling and glucose metabolism. To confirm the inhibitory effects of Morin on miR-29a, we have transfected cells with mimic and inhibitor-miR-29a. This study for the first time identifies that Morin improves diabetic condition through down regulation of the miR-29a level, and suggest that this new inhibitor of miR-29a may be a useful biomedicine to treat diabetes.

摘要

糖尿病是一种全球范围内的复杂代谢性疾病,其特征是由于胰岛素分泌受损、胰岛素作用受损或两者兼而有之导致的高血糖。微小RNA-29a是胰岛素信号通路和糖异生途径的重要调节因子,通过其在糖尿病中上调的表达发挥作用。桑色素是一种具有胰岛素模拟作用且能与核酸和蛋白质相互作用的重要生物黄酮。在本研究中,将HepG2细胞暴露于高糖环境以诱导糖尿病状态。我们确定了高糖刺激是否可能促进HepG2细胞中miR-29a的表达水平,并随后评估了桑色素对这种状态的治疗效果。在HepG2细胞中,高糖增加miR-29a表达水平并降低其靶基因的表达,增加糖异生途径中相关下游基因的表达。桑色素处理下调miR-29a表达水平并改善胰岛素信号传导和葡萄糖代谢。为了证实桑色素对miR-29a的抑制作用,我们用模拟物和抑制剂-miR-29a转染细胞。本研究首次发现桑色素通过下调miR-29a水平改善糖尿病状态,并表明这种新的miR-29a抑制剂可能是治疗糖尿病的有用生物药物。

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