胰岛素抵抗
微泡
炎症
小RNA
巨噬细胞
体内
胰岛素
2型糖尿病
内科学
葡萄糖稳态
外体
内分泌学
平衡
细胞生物学
癌症研究
下调和上调
表型
糖尿病
生物
体外
医学
免疫学
生物化学
基因
遗传学
作者
Wei Ying,Hong Gao,Felipe C.G. Reis,Gautam Bandyopadhyay,Jachelle M. Ofrecio,Z. David Luo,Yanfeng Ji,Zhongmou Jin,Crystal Ly,Jerrold M. Olefsky
出处
期刊:Cell Metabolism
[Elsevier]
日期:2021-04-01
卷期号:33 (4): 781-790.e5
被引量:151
标识
DOI:10.1016/j.cmet.2020.12.019
摘要
Insulin resistance is a major pathophysiologic defect in type 2 diabetes and obesity, while anti-inflammatory M2-like macrophages are important in maintaining normal metabolic homeostasis. Here, we show that M2 polarized bone marrow-derived macrophages (BMDMs) secrete miRNA-containing exosomes (Exos), which improve glucose tolerance and insulin sensitivity when given to obese mice. Depletion of their miRNA cargo blocks the ability of M2 BMDM Exos to enhance insulin sensitivity. We found that miR-690 is highly expressed in 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 recapitulate the 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 for metabolic disease.
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