IRS-1 IRS-2蛋白质在PCOS患者脂肪组织中的表达

目的研究多囊卵巢综合征(Polycystic ovary syndrome,PCOS)患者脂肪组织胰岛素受体底物-1(Insulin receptor substeate-1,IRS-1)及胰岛素受体底物-2(Insulin receptor substeate-2,IRS-2)蛋白的表达,探讨PCOS产生胰岛素抵抗(Insulin resistance,IR)的分子机制。方法采用放射免疫法检测PCOSIR组(20例)、PCOS非IR组(15例)及对照组(20例)血清空腹胰岛素(Fasting insulin,FIN)的浓度;采用葡萄糖氧化酶法测定血浆空腹血糖(Fasting plasma glucose,FPG);采用HOMA(Homeostasis model assessment,HOMA)模型计算胰岛素抵抗指数(HOMA-IR);采用Western blot方法检测IRS-1及IRS-2蛋白的表达。结果(1)PCOS IR组患者血清FIN及HOMA-IR均显著高于PCOS非IR组与对照组(均P<0.05);PCOS非IR组患者血清FIN及HOMA-IR亦显著高于对照组(均P<05);(2)PCOSIR组与PCOS非IR组及对照组相比,IRS-1蛋白表达量明显下降(P<0.05),而IRS-2蛋白表达无显著性差别。结论PCOS患者脂肪组织IRS-1蛋白表达的下降所导致的受体后信号转导障碍可能是其产生胰岛素抵抗的机制之一。

Protein Expression of Insulin Receptor Substrate- 1 and 2 in the Adipose Tissue from Patients with Polycystic Ovary Syndrome

Objective To investigate the protein expression of insulin receptor substrate-1 and 2 in adipose tissue from patients with polycystic ovary syndrome,and explore molecular mechanisms of insulin resistance of PCOS.Methods Samples from patients with PCOS with insulin resistance(n=20),PCOS without insulin resistance (n=15) and controls (n=20) were collected.Serum fasting insulin (FIN) was measured by radioimmunoassay.Fasting plasma glucose (FPG) was measured by oxidase assay.Insulin resistance index was calculated using homeostasis model assessment (HOMA) to analyze the relationship between these markers and insulin resistance.The abundance of insulin receptor substrate-1 and 2 in adipose tissue was assessed by Western blot.The tyrosine phosphorylation of IRS-1 was measured by immunoprecipitation and enhanced chemiluminescent immunoblotting technique.Results (1)The levels of serum FIN and HOMA-IR in PCOS without insulin resistance were significantly higher than that of control group(all P<0.05);The levels of serum FIN and HOMA-IR in PCOS with insulin resistance were significantly higher than that of PCOS without insulin resistance(all P<0.05);(2)The protein expression of IRS-1 in PCOS with insulin resistance were significantly lower than that in PCOS without insulin resistance and control group(P<0.05),but no significantly difference existed in IRS-2 expression.Conclusion The signal transduction malfunction because of decreased IRS-1 protein expression in the insulin signal transduction pathway may be one of the mechanism leading to insulin resistance.