机构：[1]Division of Endocrinology and Metabolism, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China四川大学华西医院[2]Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China四川大学华西医院[3]Department of General Surgery, Yaan People’s Hospital, Yaan, Sichuan, China[4]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China四川大学华西医院[5]Department of General Practice and Lab of PTM, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China四川大学华西医院[6]Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte, California, United States of America,[7]Division of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China四川大学华西医院
Type 2 diabetes (T2D) is characterized by insulin resistance along with pancreatic β cell failure. β cell factors are traditionally thought to control glucose homeostasis by modulating insulin levels, not insulin sensitivity. Exosomes are emerging as new regulators of intercellular communication. However, the role of β-cell-derived exosomes in metabolic homeostasis is poorly understood. Here, we report that microRNA-26a (miR-26a) in β cells not only modulates insulin secretion and β cell replication in an autocrine manner but also regulates peripheral insulin sensitivity in a paracrine manner through circulating exosomes. MiR-26a is reduced in serum exosomes of overweight humans and is inversely correlated with clinical features of T2D. Moreover, miR-26a is down-regulated in serum exosomes and islets of obese mice. Using miR-26a knockin and knockout mouse models, we showed that miR-26a in β cells alleviates obesity-induced insulin resistance and hyperinsulinemia. Mechanistically, miR-26a in β cells enhances peripheral insulin sensitivity via exosomes. Meanwhile, miR-26a prevents hyperinsulinemia through targeting several critical regulators of insulin secretion and β cell proliferation. These findings provide a new paradigm for the far-reaching systemic functions of β cells and offer opportunities for the treatment of T2D.
基金：
This work was supported by the Ministry
of Science and Technology of China
(2018ZX09201018-005 to XF), the National Natural
Science Foundation of China (91540113,
81970561, and 81570527 to XF, and 81502631 to
YT), the 1.3.5 Project for Disciplines of Excellence,
West China Hospital, Sichuan University
(ZYJC18049 to XF), and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan
University (Z20191005 to XF).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类|1 区生物学
小类|1 区生化与分子生物学1 区生物学
最新[2023]版：
大类|1 区生物学
小类|1 区生化与分子生物学1 区生物学
第一作者：
第一作者机构：[1]Division of Endocrinology and Metabolism, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Xu Haixia,Du Xiao,Xu Jia,et al.Pancreatic β cell microRNA-26a alleviates type 2 diabetes by improving peripheral insulin sensitivity and preserving β cell function.[J].PLoS biology.2020,18(2):e3000603.doi:10.1371/journal.pbio.3000603.
APA：
Xu Haixia,Du Xiao,Xu Jia,Zhang Yu,Tian Yan...&Fu Xianghui.(2020).Pancreatic β cell microRNA-26a alleviates type 2 diabetes by improving peripheral insulin sensitivity and preserving β cell function..PLoS biology,18,(2)
MLA：
Xu Haixia,et al."Pancreatic β cell microRNA-26a alleviates type 2 diabetes by improving peripheral insulin sensitivity and preserving β cell function.".PLoS biology 18..2(2020):e3000603
生物学