Seow Kok-Min, Juan Chi-Chang, Hsu Yung-Pei, Hwang Jiann-Loung, Huang Lee-Wen, Ho Low-Tone
Department of Obstetrics and Gynecology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei.
Hum Reprod. 2007 Apr;22(4):1003-10. doi: 10.1093/humrep/del466. Epub 2007 Jan 4.
Increased Ser(312) phosphorylation of insulin receptor substrate (IRS)-1 is one possible molecular mechanism of insulin resistance in polycystic ovary syndrome (PCOS). We investigated whether laparoscopic ovarian electrocautery (LOE) improved insulin sensitivity in women with PCOS and examined the underlying molecular mechanism of LOE.
Adipose tissue and blood samples from 12 women with PCOS before, and 3 months after, LOE were analysed.
Before LOE, women with PCOS were found to have significantly higher 2 h glucose, fasting and 2 h insulin levels, homeostasis model insulin resistance index and lower fasting glucose-to-insulin ratio (G(0)/I(0)) than healthy, lean, age-matched controls. Serum levels of glucose and insulin were significantly decreased, and G(0)/I(0) ratio was significantly increased 3 months after LOE. Levels of activated extracellular signal-regulated kinase 1/2 in PCOS women were higher than in controls, but were significantly decreased after LOE. Levels of insulin receptor, glucose transporter-4 and phosphatidylinositol 3-kinase were lower in PCOS patients before LOE than in controls and increased after LOE. Levels of Ser(312)-phosphorylated IRS-1 in PCOS women before LOE were higher than in controls and decreased significantly after LOE, whereas IRS-1 tyrosine phosphorylation in PCOS women before LOE was lower than in controls and increased significantly after LOE.
Over the short observation period of this study, our results demonstrated that LOE effectively ameliorated insulin resistance in women with PCOS via decreased IRS-1 Ser(312) phosphorylation.
胰岛素受体底物(IRS)-1 的丝氨酸(Ser)312 位点磷酸化增加是多囊卵巢综合征(PCOS)胰岛素抵抗的一种可能分子机制。我们研究了腹腔镜卵巢电灼术(LOE)是否能改善 PCOS 女性的胰岛素敏感性,并探讨了 LOE 的潜在分子机制。
分析了 12 名 PCOS 女性在 LOE 术前及术后 3 个月的脂肪组织和血液样本。
与健康、体型瘦且年龄匹配的对照组相比,发现 PCOS 女性在 LOE 术前的 2 小时血糖、空腹及 2 小时胰岛素水平、稳态模型胰岛素抵抗指数显著更高,而空腹血糖与胰岛素比值(G(0)/I(0))更低。LOE 术后 3 个月,血清葡萄糖和胰岛素水平显著降低,G(0)/I(0)比值显著升高。PCOS 女性中活化的细胞外信号调节激酶 1/2 水平高于对照组,但 LOE 术后显著降低。PCOS 患者在 LOE 术前胰岛素受体、葡萄糖转运蛋白 4 和磷脂酰肌醇 3-激酶水平低于对照组,LOE 术后升高。PCOS 女性在 LOE 术前 Ser(312)磷酸化的 IRS-1 水平高于对照组,LOE 术后显著降低,而 PCOS 女性在 LOE 术前 IRS-1 酪氨酸磷酸化低于对照组,LOE 术后显著升高。
在本研究的短观察期内,我们的结果表明 LOE 通过降低 IRS-1 Ser(312)磷酸化有效改善了 PCOS 女性的胰岛素抵抗。