Increased activation of nuclear factor κB triggers inflammation and insulin resistance in polycystic ovary syndrome
Increased activation of nuclear factor κB triggers inflammation and insulin resistance in polycystic ovary syndrome
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DOI：
10.1210/jc.2005-2327
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发表时间：
2006-04-01
影响因子：
5.8
通讯作者：
Kirwan, JP
中科院分区：
文献类型：
--
作者：
González, F;Rote, NS;Kirwan, JP
内容：目的：探讨高血糖对多囊卵巢综合征（PCOS）患者血清核因子-κ B（NF-κ B）B的影响（NF κ B）活化和抑制性κ B（I κ B）。设计和设置：这是一项在学术医学中心进行的前瞻性对照研究。研究人群包括16名育龄妇女PCOS（8瘦，8肥胖）和16个年龄和身体组成匹配的控制（8瘦，8肥胖）。主要结果测量：胰岛素敏感性（IS）来自2小时75克口服葡萄糖耐量试验（ISOGTT）。结果：PCOS组的ISOGTT低于对照组（3.3 ± 0.3vs.6.4 ± 0.9，P <0.004），PCOS组的ISOGTT高于对照组（3.3 ± 0.3vs.6.4 ± 0.9，P < 0.004）。瘦型和肥胖型PCOS患者核内NF κ B B的百分比变化高于瘦型对照组（42.5 +/- 19.1和54.5 +/- 12.5 vs. - 14.1 +/- 10.9，P < 0.006）。核内NF κ B B的百分比变化与葡萄糖摄入后2小时水平（r = 0.37; P < 0.04）和血浆睾酮（r = 0.49; P < 0.006）呈正相关，与ISOGTT呈负相关（r = 0.39; P < 0.04）。瘦型和肥胖型PCOS患者I κ B的百分比变化低于瘦型对照组（-22.3 +/- 3.2和-17.0 +/- 5.0 vs. 8.4 +/- 11.8，P < 0.02）。结论：在高血糖反应中，PCOS患者MNC核内NF κ B增加，I κ B减少，与肥胖无关。这可能代表了一个主要的炎症信号，有助于诱导胰岛素抵抗和高雄激素血症的PCOS。
Context: Insulin resistance and chronic low level inflammation are often present in women with polycystic ovary syndrome ( PCOS).Objective: The purpose of this study was to determine the effects of hyperglycemia on nuclear factor kappa B (NF kappa B) activation and inhibitory kappa B (I kappa B) from mononuclear cells (MNC) in PCOS.Design and Setting: This was a prospective controlled study conducted at an academic medical center.Patients: The study population consisted of 16 reproductive-age women with PCOS ( eight lean, eight obese) and 16 age- and body composition-matched controls ( eight lean, eight obese).Main Outcome Measures: Insulin sensitivity ( IS) was derived from a 2-h 75-g oral glucose tolerance test (ISOGTT). Intranuclear NF kappa B and I kappa B protein expression were quantitated from MNC obtained from blood drawn fasting and 2 h after glucose ingestion.Results: ISOGTT was lower in PCOS compared with controls (3.3 +/- 0.3 vs. 6.4 +/- 0.9, P < 0.004). The percent change in intranuclear NF kappa B was higher in lean and obese PCOS compared with lean controls (42.5 +/- 19.1 and 54.5 +/- 12.5 vs. - 14.1 +/- 10.9, P < 0.006). The percent change in intranuclear NF kappa B correlated positively with 2-h postglucose ingestion levels ( r = 0.37; P < 0.04) and plasma testosterone ( r = 0.49; P < 0.006) and correlated negatively with ISOGTT ( r = 0.39; P < 0.04). The percent change in I kappa B was lower in lean and obese PCOS compared with lean controls ( - 22.3 +/- 3.2 and - 17.0 +/- 5.0 vs. 8.4 +/- 11.8, P < 0.02).Conclusion: In response to hyperglycemia, intranuclear NF kappa B increases and I kappa B decreases in MNC of women with PCOS independent of obesity. This may represent a cardinal inflammatory signal that contributes to the induction of insulin resistance and hyperandrogenism in PCOS.