美国加州大学圣迭戈分校Jerrold M. Olefsky小组发现，MiR-690是一种M2极化型巨噬细胞外泌体来源的miRNA，可改善肥胖小鼠的胰岛素敏感性。相关论文于2021年1月14日在线发表在《细胞—代谢》杂志上。

研究人员发现，M2极化型骨髓源性巨噬细胞（BMDM）能够分泌含miRNA的外泌体（Exo），当给予肥胖小鼠时，可改善葡萄糖耐量和胰岛素敏感性。这些miRNA货物的耗竭阻碍了M2 BMDM Exo增强胰岛素敏感性的能力。研究人员发现miR-690在M2 BMDM Exo中高度表达，并且在体内和体外均起胰岛素增敏剂的作用。

在miRNA耗尽的BMDM中表达miR-690模拟物会生成Exo，并且这概括了M2 BMDM Exo对代谢表型的影响。Nadk是miR-690的真正靶标mRNA，并且Nadk在调节巨噬细胞炎症和胰岛素信号传导中起作用。

综上所述，这些数据表明miR-690可能是一种治疗代谢性疾病的新型胰岛素增敏分子。

据介绍，胰岛素抵抗是2型糖尿病和肥胖症的主要病理生理缺陷，而抗炎M2样巨噬细胞对于维持正常的代谢稳态至关重要。 

附：英文原文

Title: MiR-690, an exosomal-derived miRNA from M2-polarized macrophages, improves insulin sensitivity in obese mice

Author: Wei Ying, Hong Gao, Felipe Castellani Gomes Dos Reis, Gautam Bandyopadhyay, Jachelle M. Ofrecio, Zhenlong Luo, Yudong Ji, Zhongmou Jin, Crystal Ly, Jerrold M. Olefsky

Issue&Volume: 2021-01-14

Abstract: Insulin resistance is a major pathophysiologic defect in type 2 diabetes and obesity,while anti-inflammatory M2-like macrophages are important in maintaining normal metabolichomeostasis. Here, we show that M2 polarized bone marrow-derived macrophages (BMDMs)secrete miRNA-containing exosomes (Exos), which improve glucose tolerance and insulinsensitivity when given to obese mice. Depletion of their miRNA cargo blocks the abilityof M2 BMDM Exos to enhance insulin sensitivity. We found that miR-690 is highly expressedin M2 BMDM Exos and functions as an insulin sensitizer both in vivo and in vitro. Expressing an miR-690 mimic in miRNA-depleted BMDMs generates Exos that recapitulatethe effects of M2 BMDM Exos on metabolic phenotypes. Nadk is a bona fide target mRNA of miR-690, and Nadk plays a role in modulating macrophage inflammation and insulin signaling. Taken together,these data suggest miR-690 could be a new therapeutic insulin-sensitizing agent formetabolic disease.

DOI: 10.1016/j.cmet.2020.12.019

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30717-8