Nature：一种小核糖核酸与Ⅱ型糖尿病有关

英国最新一期《自然》杂志刊登报告说，研究人员发现了一种小核糖核酸与胰岛素耐受性相关，该发现或为开发Ⅱ型糖尿病新疗法提供思路。

德国马克斯·普朗克研究所的研究人员报告说，他们通过动物实验发现，一种名为“miR-802”的小核糖核酸分子在成年实验鼠体内的过度表达会使胰岛素敏感性受损，产生葡萄糖耐受不良，从而与过度肥胖和糖尿病等病症相关。

研究人员延斯·布吕内说，此前研究表明一些小核糖核酸可能会影响基因正常表达，从而引发过度肥胖等病症，新研究发现“miR-802”会直接影响一种名为“TCF2”的蛋白质，而肥胖人群中这种核糖核酸分子往往高出正常值。

研究人员表示，今后有望将这种小核糖核酸和蛋白质作为治疗靶点，开发出治疗糖尿病和肥胖等相关疾病的新药物。

Ⅱ型糖尿病又称成年发病型糖尿病，是最常见的糖尿病之一，其特点是胰岛素耐受性，即体内组织对胰岛素的作用不敏感，胰岛素起不到正常的降血糖作用。

doi:10.1038/nature11793
PMC:
PMID:

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

Jan-Wilhelm Kornfeld,Catherina Baitzel,A. Christine K?nner,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

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.