Soluble and Cell-Associated Insulin Receptor Dysfunction Correlates with Severity of HAND in HIV-Infected Women
Soluble and Cell-Associated Insulin Receptor Dysfunction Correlates with Severity of HAND in HIV-Infected Women
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DOI：
10.1371/journal.pone.0037358
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发表时间：
2012-05-22
期刊：
影响因子：
3.7
通讯作者：
Wojna, Valerie
中科院分区：
文献类型：
--
作者：
Gerena, Yamil;Skolasky, Richard L.;Wojna, Valerie
背景：已在HIV感染者中发现血糖代谢异常，并与HIV相关性神经认知障碍(HAND)相关。这些异常可能是由于慢性HIV感染，长期使用联合抗逆转录病毒治疗(CART)，年龄，遗传易感性，或这些因素的组合，并可能增加该人群的发病率和死亡率。目的：确定可溶性和细胞相关胰岛素受体(IR)水平、IR底物-1(IRS-1)水平的变化，和IRS-1酪氨酸磷酸化与HIV血清阳性妇女队列中手的存在和严重程度相关。方法和结果：这是一项回顾性横断面研究，使用患者数据库信息和来自西班牙裔-拉丁裔纵向妇女队列的34名HIV血清阳性妇女和10名无糖尿病病史的对照样本。用ELISA法测定血浆和脑脊液中可溶性IR亚基[SIR、胞外结构域(A)和全长或完整(Ab)]。用流式细胞仪检测脑脊液中白细胞颗粒(WCP)的膜IR、IRS-1水平和IRS-1酪氨酸磷酸化水平。HIV血清阳性妇女血浆中完整或全长SIR水平显著增加(P
Background: Blood sugar metabolism abnormalities have been identified in HIV-infected individuals and associated with HIV-associated neurocognitive disorders (HAND). These abnormalities may occur as a result of chronic HIV infection, long-term use of combined antiretroviral treatment (CART), aging, genetic predisposition, or a combination of these factors, and may increase morbidity and mortality in this population.Objective: To determine if changes in soluble and cell-associated insulin receptor (IR) levels, IR substrate-1 (IRS-1) levels, and IRS-1 tyrosine phosphorylation are associated with the presence and severity of HAND in a cohort of HIV-seropositive women.Methods and Results: This is a retrospective cross-sectional study using patient database information and stored samples from 34 HIV-seropositive women and 10 controls without history of diabetes from the Hispanic-Latino Longitudinal Cohort of Women. Soluble IR subunits [sIR, ectodomain (a) and full-length or intact (ab)] were assayed in plasma and CSF samples by ELISA. Membrane IR levels, IRS-1 levels, and IRS-1 tyrosine phosphorylation were analyzed in CSF white cell pellets (WCP) using flow cytometry. HIV-seropositive women had significantly increased levels of intact or full-length sIR in plasma (p