Natural killer cell-derived exosomal miR-1249-3p attenuates insulin resistance and inflammation in mouse models of type 2 diabetes

Abstract Natural killer (NK) cells have been suggested to be associated with type 2 diabetes by regulating systemic inflammation. However, the mechanism by which NK cells regulate insulin sensitivity remains unknown. This study shows that NK-derived exosomes from lean mice attenuate obesity-induced...

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Autores principales:	Ying Wang, Mengwei Li, Lin Chen, Huan Bian, Xiangying Chen, Huilin Zheng, Peiwei Yang, Quan Chen, Hanmei Xu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Medicine R Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0b8ec293916940849994272d638a067b
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spelling	oai:doaj.org-article:0b8ec293916940849994272d638a067b2021-12-05T12:07:21ZNatural killer cell-derived exosomal miR-1249-3p attenuates insulin resistance and inflammation in mouse models of type 2 diabetes10.1038/s41392-021-00805-y2059-3635https://doaj.org/article/0b8ec293916940849994272d638a067b2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41392-021-00805-yhttps://doaj.org/toc/2059-3635Abstract Natural killer (NK) cells have been suggested to be associated with type 2 diabetes by regulating systemic inflammation. However, the mechanism by which NK cells regulate insulin sensitivity remains unknown. This study shows that NK-derived exosomes from lean mice attenuate obesity-induced insulin resistance and inflammation in mice of type 2 diabetes. Moreover, lean NK-derived exosomes enhance insulin sensitivity and relieve inflammation in adipocytes and hepatocytes. MiR-1249-3p, which is significantly upregulated in lean NK-derived exosomes, can be transferred from NK cells to adipocytes and hepatocytes via exosomes. NK-derived exosomal miR-1249-3p dramatically induces cellular insulin sensitivity and relieves inflammation. Mechanistically, exosomal miR-1249-3p directly targets SKOR1 to regulate the formation of ternary complex SMAD6/MYD88/SMURF1, which mediates glucose homeostasis by suppressing the TLR4/NF-κB signaling pathway. This study reveals an emerging role for NK-derived exosomal miR-1249-3p in remission of insulin resistance, and provides a series of potential therapeutic targets in type 2 diabetes.Ying WangMengwei LiLin ChenHuan BianXiangying ChenHuilin ZhengPeiwei YangQuan ChenHanmei XuNature Publishing GrouparticleMedicineRBiology (General)QH301-705.5ENSignal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Biology (General) QH301-705.5
spellingShingle	Medicine R Biology (General) QH301-705.5 Ying Wang Mengwei Li Lin Chen Huan Bian Xiangying Chen Huilin Zheng Peiwei Yang Quan Chen Hanmei Xu Natural killer cell-derived exosomal miR-1249-3p attenuates insulin resistance and inflammation in mouse models of type 2 diabetes
description	Abstract Natural killer (NK) cells have been suggested to be associated with type 2 diabetes by regulating systemic inflammation. However, the mechanism by which NK cells regulate insulin sensitivity remains unknown. This study shows that NK-derived exosomes from lean mice attenuate obesity-induced insulin resistance and inflammation in mice of type 2 diabetes. Moreover, lean NK-derived exosomes enhance insulin sensitivity and relieve inflammation in adipocytes and hepatocytes. MiR-1249-3p, which is significantly upregulated in lean NK-derived exosomes, can be transferred from NK cells to adipocytes and hepatocytes via exosomes. NK-derived exosomal miR-1249-3p dramatically induces cellular insulin sensitivity and relieves inflammation. Mechanistically, exosomal miR-1249-3p directly targets SKOR1 to regulate the formation of ternary complex SMAD6/MYD88/SMURF1, which mediates glucose homeostasis by suppressing the TLR4/NF-κB signaling pathway. This study reveals an emerging role for NK-derived exosomal miR-1249-3p in remission of insulin resistance, and provides a series of potential therapeutic targets in type 2 diabetes.
format	article
author	Ying Wang Mengwei Li Lin Chen Huan Bian Xiangying Chen Huilin Zheng Peiwei Yang Quan Chen Hanmei Xu
author_facet	Ying Wang Mengwei Li Lin Chen Huan Bian Xiangying Chen Huilin Zheng Peiwei Yang Quan Chen Hanmei Xu
author_sort	Ying Wang
title	Natural killer cell-derived exosomal miR-1249-3p attenuates insulin resistance and inflammation in mouse models of type 2 diabetes
title_short	Natural killer cell-derived exosomal miR-1249-3p attenuates insulin resistance and inflammation in mouse models of type 2 diabetes
title_full	Natural killer cell-derived exosomal miR-1249-3p attenuates insulin resistance and inflammation in mouse models of type 2 diabetes
title_fullStr	Natural killer cell-derived exosomal miR-1249-3p attenuates insulin resistance and inflammation in mouse models of type 2 diabetes
title_full_unstemmed	Natural killer cell-derived exosomal miR-1249-3p attenuates insulin resistance and inflammation in mouse models of type 2 diabetes
title_sort	natural killer cell-derived exosomal mir-1249-3p attenuates insulin resistance and inflammation in mouse models of type 2 diabetes
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/0b8ec293916940849994272d638a067b
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Natural killer cell-derived exosomal miR-1249-3p attenuates insulin resistance and inflammation in mouse models of type 2 diabetes

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