Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome
Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome
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DOI：
10.1210/jc.2005-1696
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发表时间：
2006-01-01
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：多囊卵巢综合征（PCOS）女性通常存在胰岛素抵抗和慢性低水平炎症。目的：本研究的目的是确定高血糖对多囊卵巢综合征（PCOS）单核细胞（MNCs）产生活性氧簇（ROS）的影响。设计：这是一项前瞻性对照研究。设置：该研究在学术医疗中心进行。患者：研究人群包括16名PCOS患者（8名瘦，8名肥胖）和15名年龄和身体成分匹配的对照组（8名瘦，7名肥胖）。主要结果测量：胰岛素敏感性来自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（3.1 ± 0.3 vs.6.3 ± 0.9，P <0.003），PCOS组的ISOGTT低于对照组（3.1 ± 0.3 vs.6.3 ± 0.9，P < 0.003）。与瘦型对照组相比，瘦型和肥胖型PCOS患者MNC产生的ROS百分比变化更高（138.8 +/- 21.3和154.2 +/- 49.1 vs. 0.6 +/- 12.7，P < 0.003）。单核细胞活性氧产生的百分比变化与葡萄糖曲线下面积（r = 0.38，P < 0.05）、血浆睾酮（r = 0.59，P < 0.002）和雄烯二酮（r = 0.50，P < 0.009）水平呈正相关。与瘦型对照组相比，瘦型和肥胖型PCOS患者的MNC中p47（phox）的百分比变化也更高（36.2 ± 18.2和39.1 ± 8.0 vs. -13.7 ± 8.7，P < 0.02），与ISOGTT呈负相关结论：PCOS患者外周血单个核细胞在高血糖刺激下产生的ROS增加，与肥胖无关。由此产生的氧化应激可能有助于促炎状态，诱导胰岛素抵抗和高雄激素血症的妇女与这种疾病。
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 reactive oxygen species (ROS) generation from mononuclear cells (MNCs) in PCOS.Design: This was a prospective controlled study.Setting: The study was conducted at an academic medical center.Patients: The study population consisted of 16 women with PCOS (eight lean, eight obese) and 15 age- and body composition-matched controls (eight lean, seven obese).Main Outcome Measures: Insulin sensitivity was derived from a 2-h, 75-g oral glucose tolerance test (ISOGTT). ROS generation and p47(phox) protein expression were quantitated from MNCs obtained from blood drawn fasting and 2 h after glucose ingestion.Results: ISOGTT was lower in PCOS, compared with controls (3.1 +/- 0.3 vs. 6.3 +/- 0.9, P < 0.003). The percent change in ROS generation from MNCs was higher in lean and obese PCOS, compared with lean controls (138.8 +/- 21.3 and 154.2 +/- 49.1 vs. 0.6 +/- 12.7, P < 0.003). The percent change in ROS generation from MNCs correlated positively with glucose area under the curve (r = 0.38, P < 0.05), and plasma levels of testosterone (r = 0.59, P < 0.002) and androstenedione (r = 0.50, P < 0.009). The percent change in p47(phox) from MNCs was also higher in lean and obese PCOS, compared with lean controls (36.2 +/- 18.2 and 39.1 +/- 8.0 vs. -13.7 +/- 8.7, P < 0.02), and correlated negatively with ISOGTT (r = -0.39, P < 0.05).Conclusion: ROS generation from MNCs in response to hyperglycemia is increased in PCOS independent of obesity. The resultant oxidative stress may contribute to a proinflammatory state that induces insulin resistance and hyperandrogenism in women with this disorder.