MicroRNAs 103 and 107 regulate insulin sensitivity
Mirko Trajkovski,1, 2 Jean Hausser,2, 3 Jürgen Soutschek,4 Bal Bhat,4 Akinc Akin,5 Mihaela Zavolan,3 Markus H. Heim2, 6 & Markus Stoffel1, 2
Affiliations Contributions Corresponding author Journal name:
Nature Volume: 474, Pages: 649–653
Date published: (30 June 2011)
DOI: doi:10.1038/nature10112
Received 22 March 2010 Accepted 13 April 2011 Published online 08 June 2011
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Share/bookmarkConnotea Cite U Like Facebook Twitter Delicious Digg Defects in insulin signalling are among the most common and earliest defects that predispose an individual to the development of type 2 diabetes1, 2, 3. MicroRNAs have been identified as a new class of regulatory molecules that influence many biological functions, including metabolism4, 5. However, the direct regulation of insulin sensitivity by microRNAs in vivo has not been demonstrated. Here we show that the expression of microRNAs 103 and 107 (miR-103/107) is upregulated in obese mice. Silencing of miR-103/107 leads to improved glucose homeostasis and insulin sensitivity. In contrast, gain of miR-103/107 function in either liver or fat is sufficient to induce impaired glucose homeostasis. We identify caveolin-1, a critical regulator of the insulin receptor, as a direct target gene of miR-103/107. We demonstrate that caveolin-1 is upregulated upon miR-103/107 inactivation in adipocytes and that this is concomitant with stabilization of the insulin receptor, enhanced insulin signalling, decreased adipocyte size and enhanced insulin-stimulated glucose uptake. These findings demonstrate the central importance of miR-103/107 to insulin sensitivity and identify a new target for the treatment of type 2 diabetes and obesity.

Subject terms:Physiology Molecular biology Medical research Cell biology
Top of page糖尿病和肥胖症的一个新的治疗目标
Nature 474 (30 Jun 2011)

对两个肥胖症小鼠模型的肝脏所做的一个微RNA(miRNA)微阵列分析表明，miRNA-103 和 miRNA-103 107的表达水平在肥胖症中被提高。使这些miRNA沉默，可以改善葡萄糖体内平衡和提高胰岛素敏感性。激活肝脏或脂肪中的miRNA足以损害葡萄糖体内平衡。Caveolin-1（胰岛素信号作用调控中所涉及的一种蛋白）是miRNA的一个直接目标基因。这些发现表明miR-103/107调控胰岛素敏感性，同时也为2-型糖尿病和肥胖症的治疗识别出一个新的潜在目标。