ShanghaiTech University Knowledge Management System
Downregulation of miR-181a upregulates sirtuin-1 (SIRT1) and improves hepatic insulin sensitivity | |
2012 | |
发表期刊 | DIABETOLOGIA |
ISSN | 0012-186X |
卷号 | 55期号:7页码:232-243 |
发表状态 | 已发表 |
DOI | 10.1007/s00125-012-2539-8 |
摘要 | Sirtuin-1 (SIRT1) is a potential therapeutic target to combat insulin resistance and type 2 diabetes. This study aims to identify a microRNA (miRNA) targeting SIRT1 to regulate hepatic insulin sensitivity. Luciferase assay combined with mutation and immunoblotting was used to screen and verify the bioinformatically predicted miRNAs. miRNA and mRNA levels were measured by real-time PCR. Insulin signalling was detected by immunoblotting and glycogen synthesis. Involvement of SIRT1 was studied with adenovirus, inhibitor and SIRT1-deficient hepatocytes. The role of miR-181a in vivo was explored with adenovirus and locked nucleic acid antisense oligonucleotides. miR-181a targets the 3' untranslated region (3'UTR) of Sirt1 mRNA through a miR-181a binding site, and downregulates SIRT1 protein abundance at the translational level. miR-181a is increased in insulin-resistant cultured hepatocytes and liver, and in the serum of diabetic patients. Overexpression of miR-181a decreases SIRT1 protein levels and activity, and causes insulin resistance in hepatic cells. Inhibition of miR-181a by antisense oligonucleotides increases SIRT1 protein levels and activity, and improves insulin sensitivity in hepatocytes. Ectopic expression of SIRT1 abrogates the effect of miR-181a on insulin sensitivity, and inhibition of SIRT1 activity or SIRT1 deficiency markedly attenuated the improvement in insulin sensitivity induced by antisense miR-181a. In addition, overexpression of miR-181a by adenovirus impairs hepatic insulin signalling, and intraperitoneal injection of locked nucleic acid antisense oligonucleotides for miR-181a improves glucose homeostasis in diet-induced obesity mice. miR-181a regulates SIRT1 and improves hepatic insulin sensitivity. Inhibition of miR-181a might be a potential new strategy for treating insulin resistance and type 2 diabetes. |
关键词 | Hepatocytes Insulin resistance Locked nucleic acid MicroRNA |
URL | 查看原文 |
收录类别 | SCI |
WOS研究方向 | Endocrinology & Metabolism |
WOS类目 | Endocrinology & Metabolism |
WOS记录号 | WOS:000305215200022 |
出版者 | SPRINGER |
WOS关键词 | CELL-DIFFERENTIATION ; 3T3-L1 ADIPOCYTES ; SIGNALING PATHWAY ; RAT MODEL ; MICRORNA ; RESISTANCE ; MICE ; EXPRESSION ; DISEASE ; TARGET |
原始文献类型 | Article |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/119849 |
专题 | 个人在本单位外知识产出 |
通讯作者 | Zhai, Q. W. |
作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai 200031, Peoples R China 2.Shanghai Jiao Tong Univ, Sch Med, Shanghai 200030, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai 200031, Peoples R China 4.Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China |
推荐引用方式 GB/T 7714 | Zhou, B.,Li, C.,Qi, W.,et al. Downregulation of miR-181a upregulates sirtuin-1 (SIRT1) and improves hepatic insulin sensitivity[J]. DIABETOLOGIA,2012,55(7):232-243. |
APA | Zhou, B..,Li, C..,Qi, W..,Zhang, Y..,Zhang, F..,...&Zhai, Q. W..(2012).Downregulation of miR-181a upregulates sirtuin-1 (SIRT1) and improves hepatic insulin sensitivity.DIABETOLOGIA,55(7),232-243. |
MLA | Zhou, B.,et al."Downregulation of miR-181a upregulates sirtuin-1 (SIRT1) and improves hepatic insulin sensitivity".DIABETOLOGIA 55.7(2012):232-243. |
条目包含的文件 | 下载所有文件 | |||||
文件名称/大小 | 文献类型 | 版本类型 | 开放类型 | 使用许可 |
个性服务 |
查看访问统计 |
谷歌学术 |
谷歌学术中相似的文章 |
[Zhou, B.]的文章 |
[Li, C.]的文章 |
[Qi, W.]的文章 |
百度学术 |
百度学术中相似的文章 |
[Zhou, B.]的文章 |
[Li, C.]的文章 |
[Qi, W.]的文章 |
必应学术 |
必应学术中相似的文章 |
[Zhou, B.]的文章 |
[Li, C.]的文章 |
[Qi, W.]的文章 |
相关权益政策 |
暂无数据 |
收藏/分享 |
修改评论
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。