多囊卵巢综合征合并胰岛素抵抗患者脂肪组织中磷脂酰肌醇3激酶的检测及其意义

目的检测多囊卵巢综合征(PCOS)合并胰岛素抵抗(IR)患者脂肪组织中磷脂酰肌醇3激酶(PI-3K)的表达,探讨PCOS患者发生IR的机制。方法检测PCOS发生IR 19例患者(PCOS IR组)、PCOS未发生IR 10例患者(PCOS非IR组)及因单纯子宫肌瘤施行手术的15例患者(对照组)的空腹血清胰岛素(FIN)及空腹血糖(FPG)的水平。采用稳态模型(HOMA)法评价及计算IR指数(HOMA-IR);采用蛋白印迹法检测脂肪组织中PI-3K蛋白的表达;采用RT-PCR技术检测PI-3K mRNA的表达;采用免疫沉淀技术、薄层层析及γ液体闪烁计数仪检测PI-3K的活性,设对照组平均PI-3K活性为100%。结果(1)PCOS IR组患者血清FIN为(25．2±3．8)mU/L,HOMA-IR为1．6±0．3;PCOS非IR组分别为(13．4±3．8)mU/L及0．9±0．3;对照组分别为(9．5±2．6)mU/L及0．5±0．3,3组分别比较,差异均有统计学意义(P＜0．05)。(2)PCOS IR组PI-3K蛋白及mRNA相对表达水平分别为0．65±0．10及0．92±0．12;PCOS非IR组分别为0．72±0．10及1．01±0．10;对照组分别为0．73±0．14及1．00±0．12,3组分别比较,差异均无统计学意义(P＞0．05)。(3)PCOS IR组PI- 3K活性下降为81%,PCOS非IR组下降为89%,PCOS IR组及PCOS非IR组分别与对照组比较,差异均有统计学意义(P＜0．01,P＜0．05)。PCOS IR组和PCOS非IR组PI-3K活性与HOMA-IR均呈显著负相关关系(r=-0．69,P＜0．01;r=-0．62,P＜0．05)。结论PCOS IR患者的PI-3K蛋白及mRNA的表达无明显改变,但PCOS患者PI-3K活性降低,可能是PCOS患者发生IR的机理之一。     

磷脂酰肌醇-3激酶活性在妊娠期糖尿病患者脂肪组织中的检测

目的检测妊娠期糖尿病(gestational diabetes mellitus,GDM)患者脂肪组织磷脂酰肌醇-3激酶(phosphatidylinositol 3-kinase,PI-3K)活性的改变,探讨GDM产生胰岛素抵抗(insulin resistance,IR)的分子机制。方法采用放射免疫法测定35例正常妊娠妇女及35例GDM患者血清空腹胰岛素(fasting insu-lin,FIN)的浓度,葡萄糖氧化酶法测定血浆空腹血糖(fasting plasma glucose,FPG);免疫沉淀、薄层层析及γ液闪计数方法检测PI-3激酶的活性,并进行分析比较。结果 GDM组患者FPG[(7.85±3.51)mmol/L]、FIN[(25.17±3.76)mU/L]及HOMA-IR(1.75±0.12)均显著高于对照组,差异有统计学意义(P均0.01);与对照组比较,GDM组PI-3K活性(85.75%)下降(P0.01);GDM组PI-3K与孕晚期体重、孕晚期体重指数及HOMA-IR呈负相关(r=-0.59、r=-0.63、r=-0.74,P均0.01)。结论 GDM患者PI-3K参与了胰岛素信号通路中信号分子的生物学作用,导致IR的形成。     

多囊卵巢综合征患者胰岛素抵抗与脂代谢的关系

目的:探讨多囊卵巢综合征(PCOS)患者胰岛素抵抗(IR)、肥胖及血脂代谢的关系。方法:把PCOS病人分成IR组(15例),非IR组(25例),另设正常育龄妇女为对照组(20例)三组,检测空腹血甘油三脂(TG)、总胆固醇(TC)、载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、葡萄糖耐量试验(OGTT)、胰岛素(INS)释放试验,并计算体重指数(BMI)和腰臀比(WHR)。结果:(1)BMI、WHR三组间差别有显著意义(P<0.05,P0.05),后者三组间差别有显著意义(P<0.05)。结论:PCOS病人的IR与肥胖及脂代谢关系密切,使发生心血管疾病风险增加。     

瘦素与多囊卵巢综合征

<正>多囊卵巢综合征(polycystic ovarian syndrome,PCOS)是一组发病多因性、临床表现异质性的综合征,典型临床特征是雄激素过多和长期无排卵。是育     

磷脂酰肌醇-3激酶的表达及其活性变化与妊娠期糖尿病胰岛素抵抗的关系

目的 研究磷脂酰肌醇-3激酶(phosphatidyl inositol-3 kinase,PI-3K)在妊娠期糖尿病(gestational diabetes mellitus,GDM)患者脂肪组织中的表达及其活性变化,分析其与GDM胰岛素抵抗(insulin resistance,IR)的关系.方法 采用Western印迹法、RT-PCR法分别检测20例GDM孕妇(GDM组)和20例正常妊娠晚期孕妇(正常妊娠组)脂肪组织中PI-3K p85α蛋白质和mRNA的表达,采用ELISA法检测两组孕妇脂肪组织中PI-3K的活性,葡萄糖氧化酶法和放射免疫法检测两组孕妇空腹血糖(fasting plasma glucose,FPG)及空腹胰岛素(fasting insulin,FIN)水平,并采用稳态模型(homeostasis model assessment,HOMA)计算IR指数.结果 (1)PI-3K p85a蛋白的表达GDM组高于正常妊娠组(0.93±0.04和0.71±0.06,P＜0.01).(2)GDM组PI-3K p85emRNA表达高于正常妊娠组(0.83±0.03和0.53±0.07,P＜0.01).(3)GDM组PI-3K的活性为正常妊娠组的30%,明显降低(1.7±0.6和5.2±0.5,P＜0.01)(4)GDM组FPG、FINS、HOMA-IR分别为(5.8±0.2)mmol/L、(14.8±0.2)mmol/L和1.3±0.4,正常晚孕组分别为(4.7±0.3)mmol/L、(11.2±0.3)mmol/L和0.9±0.3,两组间各指标比较均有统计学意义(P＜0.01).PI-3K活性与HOMA-IR呈负相关(r=-0.68,P＜0.01).结论 GDM患者脂肪组织中PI-3K活性降低是其发生胰岛素抵抗的分子机制之一.     

多囊卵巢综合征患者的胰岛素抵抗

多囊卵巢综合征（peOS）是女性常见的生殖功能障碍性疾病,主要表现为卵巢的雄激素过多及无排卵,其发生率占生育年龄妇女的5％－10％卜］。此外,PCOS患者也存在糖代谢异常,主要表现为胰岛素抵抗（IR）及代偿性高胰岛素血症,其糖耐量低减的发生率也占生育年龄妇女的10％［'］。现就关于poOS的IR基础及临床方面研究进展作一综述。一、胰岛素作用及IR（一）胰岛素作用的细胞机理胰岛素是人体最重要的代谢激素,也是唯一降糖激素。胰岛素的生物学作用主要是调节糖代谢和脂代谢,还通过调控基因表达和蛋白质合成等进一步影响相应器官的…     

细胞信号转导信使磷脂酰肌醇3-激酶和卵巢癌的关系

磷脂酰肌醇3-激酶(PI3K)是一种与细胞信号转导有关的脂类第二信使.在人类肿瘤中,已发现PI3K级联信号途径的各成员具有基因结构,蛋白质表达和激酶活性等的异常改变.PI3K在卵巢癌中有异常表达,为肿瘤早期诊断、开发新的抗肿瘤药物和寻找新的基因治疗靶点提供了新的思路.     

磷脂酰肌醇细胞信号转导通路与妊娠期糖尿病

妊娠期胰岛素抵抗（IR）易导致妊娠期糖尿病,胰岛素通过与其受体结合可在不同组织细胞内激活不同的信号途径而产生不同的作用。因而信号转导的不同环节出现异常均可导致IR。作为胰岛素信号转导中的关键酶,磷脂酰肌醇3激酶（phosphatidylinositol3-kinase,PI3K）在调节糖代谢中起到重要作用。PI3K信号通路减弱或受阻,使胰岛素生理作用减弱,导致IR形成,进一步发展为妊娠期糖尿病。针对此信号通路的深入研究有利于进一步阐明妊娠期糖尿病的发病机制并为临床治疗提供新思路。     

磷脂酰肌醇细胞信号转导通路与妊娠期糖尿病

妊娠期胰岛素抵抗（IR）易导致妊娠期糖尿病,胰岛素通过与其受体结合可在不同组织细胞内激活不同的信号途径而产生不同的作用。因而信号转导的不同环节出现异常均可导致IR。作为胰岛素信号转导中的关键酶,磷脂酰肌醇3激酶（phosphatidylinositol3-kinase,PI3K）在调节糖代谢中起到重要作用。PI3K信号通路减弱或受阻,使胰岛素生理作用减弱,导致IR形成,进一步发展为妊娠期糖尿病。针对此信号通路的深入研究有利于进一步阐明妊娠期糖尿病的发病机制并为临床治疗提供新思路。     

细胞信号转导信使磷脂酰肌醇3—激酶和卵巢癌的关系

磷脂酰肌醇3-激酶(PI3K)是一种与细胞信号转导有关的脂类第二信使。在人类肿瘤中，已发现PI3K级联信号途径的各成员具有基因结构，蛋白质表达和激酶活性等的异常改变。PI3K在卵巢癌中有异常表达，为肿瘤早期诊断、开发新的抗肿瘤药物和寻找新的基因治疗靶点提供了新的思路。     

脂肪组织中胰岛素受体底物1蛋白的表达及酪氨酸磷酸化在多囊卵巢综合征发病中的作用

目的探讨多囊卵巢综合征(PCOS)患者脂肪组织胰岛素受体底物1(IRS1)的蛋白表达及酪氨酸磷酸化在PCOS发病中的作用。方法采用免疫沉淀法、Western印迹法和增强化学发光蛋白免疫印迹法及图像分析半定量检测24例PCOS患者[PCOS组,根据体重指数分为肥胖(体重指数≥24kg/m2)和非肥胖(体重指数<24kg/m2)者各12例]及同期因卵巢囊肿或输卵管阻塞行开腹手术的非PCOS患者24例(对照组,根据体重指数分为肥胖和非肥胖者各12例)的脂肪组织中IRS1的蛋白表达及酪氨酸磷酸化程度。结果PCOS组肥胖者IRS1的蛋白表达为(82±15)%,PCOS组非肥胖者为(79±18)%;对照组肥胖者为(75±19)%,对照组非肥胖者为(70±19)%,各组间比较,差异均无统计学意义(P>005)。脂肪组织中IRS1的酪氨酸磷酸化程度在PCOS组肥胖者为(52±23)%,对照组非肥胖者为(88±12)%,两者比较,差异有统计学意义(P<001);对照组肥胖者为(45±22)%,PCOS组非肥胖者为(70±25)%,与对照组非肥胖者比较,明显降低,差异均有统计学意义(P<001,P<005);PCOS组肥胖者和对照组肥胖者间以及PCOS组肥胖者和PCOS组非肥胖者间比较,差异均无统计学意义(P>005)。结论PCOS组脂肪组织IRS1的蛋白表达及酪氨酸磷酸化程度明显减弱,可能参与胰岛素受体后信号传导抑制,并与PCOS胰岛素抵抗的发生有     

Leptin levels and adipose tissue percentage in adolescents with polycystic ovary syndrome

Abstract

The main purpose of the research is to compare serum leptin (Lep) levels and adipose tissue percentage in adolescents diagnosed with polycystic ovary syndrome (PCOS) and those in healthy subjects. The results showed a greater percentage of patients with increased adipose tissue and significantly higher serum Lep levels in the PCOS group compared to the healthy controls. It was proved that there is a correlation between Lep and body mass index, body adipose tissue, waist circumference and HOMA index. PCOS in adolescents is a condition related to highly predominant overweight and obesity with exceeding level of body adipose tissue and higher serum Lep levels compared to healthy age-matched controls.     

The relationship between epicardial fat tissue thickness and visceral adipose tissue in lean patients with polycystic ovary syndrome

Background

Polycystic ovary syndrome (PCOS) is related to metabolic syndrome, insulin resistance, and cardiovascular metabolic syndromes. This is particularly true for individuals with central and abdominal obesity because visceral abdominal adipose tissue (VAAT) and epicardial adipose tissue (EAT) produce a large number of proinflammatory and proatherogenic cytokines. The present study aimed to determine whether there are changes in VAAT and EAT levels which were considered as indirect predictors for subclinical atherosclerosis in lean patients with PCOS.

Methods

The clinical and demographic characteristics of 35 patients with PCOS and 38 healthy control subjects were recorded for the present study. Additionally, the serum levels of various biochemical parameters were measured and EAT levels were assessed using 2D-transthoracic echocardiography.

Results

There were no significant differences in mean age (p?=?0.056) or mean body mass index (BMI) (p?=?0.446) between the patient and control groups. However, the body fat percentage, waist-to-hip ratio, amount of abdominal subcutaneous adipose tissue, and VAAT thickness were higher in the PCOS patient group than in the control group. The amounts of EAT in the patient and control groups were similar (p?=?0.384). EAT was correlated with BMI, fat mass, waist circumference, and hip circumference but not with any biochemical metabolic parameters including the homeostasis model assessment of insulin resistance index or the levels of triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein (HDL) cholesterol. However, there was a small positive correlation between the amounts of VAAT and EAT. VAAT was directly correlated with body fat parameters such as BMI, fat mass, and abdominal subcutaneous adipose thickness and inversely correlated with the HDL cholesterol level.

Conclusions

The present study found that increased abdominal adipose tissue in patients with PCOS was associated with atherosclerosis. Additionally, EAT may aid in the determination of the risk of atherosclerosis in patients with PCOS because it is easily measured.

     

The relationship between epicardial adipose tissue thickness and oxidative stress parameters in patients with isolated polycystic ovary syndrome

Abstract

Purpose: The aim of this study is to evaluate the correlation between epicardial adipose tissue thickness and oxidative stress parameters in patients with polycystic ovarian syndrome.

Methods: The study included 35 patients with PCOS and 35 healthy women. Transthoracic echocardiography was used to measure the epicardial adipose tissue thickness (EATT) of all patients. For all patients, serum TOS, TAS, hs-CRP, and insulin levels were measured according to the literature, and the HOMA-IR values were calculated. Independent samples t-test, Pearson’s correlation analysis, multivariate logistic regression analysis, and receiver operator characteristic curve (ROC) analysis were used in the statistical analysis.

Results: Between the patient group and the control group, EATT was significantly higher in the PCOS group compared to the control group (5.4?±?1.4?mm and 3.9?±?1.6?mm, respectively; p?<?0.001). Similarly, TOS, TAS, and hs-CRP levels were significantly higher in the PCOS group compared to the control group (p?<?0.01 for all). The correlation analysis showed a significant positive correlation between EATT and TAS and hs-CRP (r?=?0.349, p?<?0.01 and r?=?0.352, p?<?0.01, respectively). Multivariate regression analysis showed a significant correlation between PCOS and EATT, TAS, and diastolic blood pressure (p?<?0.05 for all).

Conclusions: Epicardial adipose tissue may play a major role in PCOS pathogenesis by leading to an increase in oxidative stress.     

多囊卵巢综合征合并胰岛素抵抗患者脂肪组织胰岛素受体底物2蛋白的表达及酪氨酸磷酸化的研究

目的检测多囊卵巢综合征(PCOS)患者脂肪组织胰岛素受体底物(IRS)2蛋白表达及其酪氨酸磷酸化的程度,探讨发生PCOS合并胰岛素抵抗(IR)的机制。方法采用蛋白印迹(Westernblot)法,检测PCOS合并IR患者19例(PCOS合并IR组)、PCOS非IR患者17例(PCOS非IR组)及因单纯子宫肌瘤行子宫切除术的患者20例(对照组)的IRS2蛋白的表达;并采用免疫组化技术,检测IRS2在脂肪组织中的分布;采用免疫沉淀及增强化学发光法,检测IRS2的酪氨酸磷酸化程度。结果(1)PCOS合并IR组、PCOS非IR组及对照组IRS2蛋白表达分别为115±026、113±026及100±025,3组比较,差异无统计学意义(P>005)。(2)PCOS合并IR组、PCOS非IR组及对照组IRS2蛋白酪氨酸磷酸化程度分别为077±016、091±025及100±012,3组比较,差异有统计学意义(P<005);PCOS非IR组与对照组比较,差异无统计学意义(P>005)。结论PCOS合并IR患者脂肪组织的IRS2蛋白酪氨酸磷酸化程度的降低,可能是发生IR的机制之一。     

Polycystic ovary syndrome,adipose tissue and metabolic syndrome

Purpose

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder that affects women of reproductive age and is characterized by ovulatory dysfunction and/or androgen excess or polycystic ovaries. Women with PCOS present a number of systemic symptoms in addition to those related to the reproductive system. It has been associated with functional derangements in adipose tissue, metabolic syndrome, type 2 diabetes, and an increased risk of cardiovascular disease (CVD).

Methods

A detailed literature search on Pubmed was done for articles about PCOS, adipokines, insulinresistance, and metabolic syndrome. Original articles, reviews, and meta-analysis were included.

Results

PCOS women are prone to visceral fat hypertrophy in the presence of androgen excess and the presence of these conditions is related to insulin resistance and worsens the PCO phenotype. Disturbed secretion of many adipocyte-derived substances (adipokines) is associated with chronic low-grade inflammation and contributes to insulin resistance. Abdominal obesity and insulin resistance stimulate ovarian and adrenal androgen production, and may further increase abdominal obesity and inflammation, thus creating a vicious cycle.

Conclusion

The high prevalence of metabolic disorders mainly related to insulin resistance and CVD risk factors in women with PCOS highlight the need for early lifestyle changes for reducing metabolic risks in these patients.

     

PCOS患者脂肪组织IRS-1、IRS-2蛋白表达及其酪氨酸磷酸化的研究

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 substrate-1,IRS-1)及胰岛素受体底物-2(insulin recep-tor substrate-2,IRS-2)蛋白的表达及其酪氨酸磷酸化,探讨PCOS产生胰岛素抵抗(insulinresistance,IR)的分子机制。方法:用放射免疫法检测各实验组血清促黄体生成素(luteini-zing hormone,LH)、促卵泡激素(follicle stimulating hormone,FSH)、睾酮(testosterone,T)、血清空腹胰岛素(fasting insulin,FIN)的水平;用葡萄糖氧化酶法测定血浆空腹血糖(fast-ing plasma glucose,FPG);用HOMA(homeostasis model assessment,HOMA)模型计算胰岛素抵抗指数(HOMA-IR);用Western blot检测IRS-1及IRS-2蛋白的表达,应用免疫沉淀及增强化学发光法检测二者的酪氨酸磷酸化程度。结果:(1)PCOS IR组患者血清LH、LH/FSH、T、FIN及HOMA-IR均显著高于PCOS非IR组与对照组(均P(0.05);(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),IRS-2蛋白表达差异无统计学意义(P>0.05);(3)PCOS IR组IRS-1及IRS-2蛋白质酪氨酸磷酸化程度显著降低(均P(0.05)。结论:PCOS患者脂肪组织IRS-1蛋白表达下降,IRS-1及IRS-2蛋白质酪氨酸磷酸化程度降低,由此导致的受体后信号转导障碍可能是产生胰岛素抵抗的机制之一。