Fetuin-B与胰岛素受体-β相互作用并促进视网膜细胞的胰岛素抗性

IF 5 2区 医学 Q1 OPHTHALMOLOGY
Wenyi Zhang, Xin Wang, Shuwei Tian, Jianming Wang, Aiyi Zhou
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引用次数: 0

摘要

目的:本研究旨在探讨糖尿病视网膜病变(DR)中胰岛素与Fetuin-B(FETUB)之间的相关性以及FETUB对胰岛素信号通路的影响:方法:采用酶联免疫吸附试验(ELISA)分析DR患者和健康对照组血清和水样中的FETUB和胰岛素水平。定量 PCR(q-PCR)、Western 印迹和 ELISA 被用来检测胰岛素刺激下 FETUB 在 ARPE-19、BV2 和 Müller 细胞中的表达。共免疫沉淀用于研究 FETUB 与胰岛素受体-β(IRβ)的相互作用。用FETUB重组蛋白或FETUB短发夹RNA(shRNA)处理胰岛素抵抗(IR)-BV2和IR-Müller细胞,以探讨FETUB对DR中胰岛素信号通路的影响。LY294002(PI3K通路抑制剂)用于确定FETUB是否通过PI3K/Akt通路影响葡萄糖代谢:结果:在水液中,FETUB的浓度与胰岛素水平呈正相关。在胰岛素调节下,FETUB在Müller细胞和BV2细胞中的表达增加,FETUB在视网膜细胞和小鼠视网膜中与IRβ相互作用。在高糖条件下,BV2和Müller细胞中IRβ与FETUB的相互作用比对照组增加。在FETUB重组蛋白处理的BV2和Müller细胞中,胰岛素信号通路的激活被抑制,但在FETUB shRNA转染的细胞中则有所增加。FETUB shRNA 无法逆转 LY294002- 介导的葡萄糖转运体-4 表达抑制:结论:视网膜细胞是胰岛素调控的 FETUB 的来源。结论:视网膜细胞是胰岛素调控 FETUB 的来源,FETUB 与 IRβ 相互作用,影响 BV2 和 Müller 细胞的胰岛素信号通路。FETUB 可通过 PI3K/Akt 通路加重 BV2 和 Müller 细胞中的 IR。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Fetuin-B Interacts With Insulin Receptor-β and Promotes Insulin Resistance in Retina Cells.

Purpose: The purpose of this study was to investigate the correlation between insulin and Fetuin-B (FETUB) and the influence of FETUB on insulin signaling pathway in diabetic retinopathy (DR).

Methods: Enzyme-linked immunosorbent assay (ELISA) was used to analyze FETUB and insulin levels in the serum and aqueous fluid of patients with DR and healthy controls. Quantitative PCR (q-PCR), Western blotting, and ELISA were used to examine FETUB expression in ARPE-19, BV2, and Müller cells under insulin stimulation. Co-immunoprecipitation was used to investigate the interaction of FETUB with insulin receptor-β (IRβ). Insulin resistance (IR)-BV2 and IR-Müller cells were treated with FETUB recombinant protein or FETUB short hairpin RNA (shRNA) to explore the influence of FETUB on insulin signaling pathway in DR. LY294002 (a PI3K pathway inhibitor) was used to determine whether FETUB affects glucose metabolism via the PI3K/Akt pathway.

Results: In aqueous fluid, FETUB concentrations were positively correlated with insulin levels. FETUB expression increased in Müller and BV2 cells under insulin regulation, and FETUB interacted with IRβ in retinal cells and mice retina. The interaction between IRβ and FETUB increased in BV2 and Müller cells under high-glucose than in controls. Insulin signaling pathway activation was suppressed in FETUB recombinant protein-treated BV2 and Müller cells but increased in FETUB shRNA-transfected cells. FETUB shRNA could not reverse LY294002-mediated inhibition of glucose transporter-4 expression.

Conclusions: Retinal cells are the source of insulin-regulated FETUB. The FETUB interacts with IRβ and affects insulin signaling pathway in BV2 and Müller cells. FETUB may aggravate IR in BV2 and Müller cells via the PI3K/Akt pathway.

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来源期刊
CiteScore
6.90
自引率
4.50%
发文量
339
审稿时长
1 months
期刊介绍: Investigative Ophthalmology & Visual Science (IOVS), published as ready online, is a peer-reviewed academic journal of the Association for Research in Vision and Ophthalmology (ARVO). IOVS features original research, mostly pertaining to clinical and laboratory ophthalmology and vision research in general.
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