首页>>文献首页>>文献正文

Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b

renchunxiao 添加于 2013/2/18 13:22:15  1230次阅读 | 1次推荐 | 0个评论

Insulin resistance represents a hallmark during the development of type 2 diabetes mellitus and in the pathogenesis of obesity-associated disturbances of glucose and lipid metabolism1, 2, 3. MicroRNA (miRNA)-dependent post-transcriptional gene silencing has been recognized recently to control gene expression in disease development and progression, including that of insulin-resistant type 2 diabetes. The deregulation of miRNAs miR-143 (ref. 4), miR-181 (ref. 5), and miR-103 and miR-107 (ref. 6) alters hepatic insulin sensitivity. Here we report that the expression of miR-802 is increased in the liver of two obese mouse models and obese human subjects. Inducible transgenic overexpression of miR-802 in mice causes impaired glucose tolerance and attenuates insulin sensitivity, whereas reduction of miR-802 expression improves glucose tolerance and insulin action. We identify Hnf1b (also known as Tcf2) as a target of miR-802-dependent silencing, and show that short hairpin RNA (shRNA)-mediated reduction of Hnf1b in liver causes glucose intolerance, impairs insulin signalling and promotes hepatic gluconeogenesis. In turn, hepatic overexpression of Hnf1b improves insulin sensitivity in Leprdb/db mice. Thus, this study defines a critical role for deregulated expression of miR-802 in the development of obesity-associated impairment of glucose metabolism through targeting of Hnf1b, and assigns Hnf1b an unexpected role in the control of hepatic insulin sensitivity.

作 者:Jan-Wilhelm Kornfeld, Catherina Baitzel, A. Christine Könner, Hayley T. Nicholls, Merly C. Vogt, Karolin Herrmanns, Ludger Scheja, Cécile Haumaitre, Anna M. Wolf, Uwe Knippschild, Jost Seibler, Silvia Cereghini, Joerg Heeren, Markus Stoffel & Jens C. Brüning
期刊名称: nature
期卷页: 第卷 第期 ~页
学科领域:医学科学 » 泌尿系统 » 泌尿系统结构、功能与发育异常
添加人是否为作者:
原文链接:http://www.nature.com/nature/journal/v494/n7435/full/nature11793.html
DOI:
ISBN:
关键词:
备 注:
来自论坛的回复:
文献笔记

   
导出选项:

评论 (0 个评论)

Page 1 of 1
<<<[1]>>>

举报 | Archiver | 科学网( 京ICP备07017567 )

GMT+8, 2011-2-15 11:31

Powered by ScienceNet.cn

Copyright © 2007- 科学时报社