Circulating exosome-like vesicles of humans with nondiabetic obesity impaired islet β-cell proliferation, which was associated with decreased Omentin-1 protein cargo.
(2022) Genes & diseases — Vol. 9, n° 4, p. 1099-1113 (2022)
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- 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 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 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.
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Ge, Q., Xie, X., Chen, X., Huang, R., Rui, C.-X., Zhen, Q., Hu, R., Wu, M., Xiao, X., & Li, X. (2022). Circulating exosome-like vesicles of humans with nondiabetic obesity impaired islet β-cell proliferation, which was associated with decreased Omentin-1 protein cargo. Genes & diseases, 9(4), 1099-1113. https://doi.org/10.1016/j.gendis.2020.12.011 (Original work published 2022)