@article{Ge2022, 
author = {Qian Ge and Xinxin Xie and Xiangjun Chen and Rongfeng Huang and Cheng-Xue Rui and Qianna Zhen and Renzhi Hu and Min Wu and Xiaoqiu Xiao and Xi Li},
title = {Circulating exosome-like vesicles of humans with nondiabetic obesity impaired islet β-cell proliferation, which was associated with decreased Omentin-1 protein cargo},
year = {2022},
journal = {Genes & Diseases},
volume = {9},
number = {4},
pages = {1099-1113},
keywords = {β-Cell, Exosome, Obesity, Proliferation, Type 2 diabetes mellitus},
url = {https://www.sciopen.com/article/10.1016/j.gendis.2020.12.011},
doi = {10.1016/j.gendis.2020.12.011},
abstract = {The regulation of β-cell mass in the status of nondiabetic obesity remains not well understood. We aimed to investigate the role of circulating exosome-like vesicles (ELVs) isolated from humans with simple obesity in the regulation of islet β-cell mass. Between June 2017 and July 2019, 81 subjects with simple obesity and 102 healthy volunteers with normal weight were recruited. ELVs were isolated by ultra-centrifugation. The proliferations of β-cells and islets were measured by 5-ethynl-2′-deoxyuridine (EdU). Protein components in ELVs were identified by Quantitative Proteomic Analysis and verified by Western blot and ELISA. The role of specific exosomal protein was analyzed by gain-of-function approach in ELVs released by 3T3-L1 preadipocytes. Circulating ELVs from subjects with simple obesity inhibited β-cell proliferation in vitro without affecting its apoptosis, secretion, and inflammation. The protein levels of Rictor and Omentin-1 were downregulated in circulating ELVs from subjects with simple obesity and associated with the obesity-linked pathologic conditions. The ELV-carried Omentin-1 and Omentin-1 protein per se were validated to increase β-cell proliferation and activate Akt signaling pathway. Moreover, Omentin-1 in ELVs was downregulated by insulin. The circulating ELVs may act as a negative regulator for β-cell mass in nondiabetic obesity through inhibiting β-cell proliferation. This effect was associated with downregulated Omentin-1 protein in ELVs. This newly identified ELV-carried protein could be a mediator linking insulin resistance to impaired β-cell proliferation and a new potential target for increasing β-cell mass in obesity and T2DM.}
}