2型糖尿病患者皮下、大网膜脂肪组织脂联素mRNA表达的定量研究

目的　探讨 2型糖尿病患者皮下及大网膜脂肪组织脂联素 (adiponectin)表达水平及与血脂联素、体重指数、腰臀比 (WHR)、胰岛素敏感性的相关关系。方法　用实时荧光定量RT PCR检测 2型糖尿病患者和非糖尿病患者皮下及大网膜脂肪组织脂联素mRNA的表达水平 ,用ELISA方法测定血浆脂联素水平。结果　 2型糖尿病患者大网膜脂肪组织脂联素mRNA表达水平较非糖尿病组显著下降 (P <0 .0 5 ) ;糖尿病组与非糖尿病组的血浆脂联素水平差异无显著性 ;糖尿病组大网膜脂肪组织脂联素mRNA表达与WHR成负相关 (r=- 0 .5 1,P <0 .0 5 )。糖尿病组血浆脂联素水平与大网膜脂肪组织脂联素mRNA的表达成正相关 (r=0 .5 7,P <0 .0 1)。结论　 2型糖尿病患者大网膜脂肪组织脂联素mRNA表达显著降低。内脏脂肪组织脂联素mRNA的表达水平可以作为胰岛素抵抗的重要参数。     

妊娠期糖尿病患者脂肪组织脂联素mRNA表达与胰岛素抵抗的关系

目的 探讨妊娠期糖尿病（GDM）患者脂肪组织脂联素mRNA表达与胰岛素抵抗（IR）的关系.方法 检测GDM患者（GDM组） 的皮下与网膜脂肪脂联素mRNA、血脂、空腹胰岛素（FINS）、游离脂肪酸（FFA）及胰岛素抵抗指数（HOMA-IR）等,并与正常孕妇（NGT组）和非育龄择期手术者（对照组）进行比较.结果 GDM组、NGT组和对照组的皮下脂肪脂联素mRNA表达均高于其网膜脂肪水平;对照组、NGT组、GDM组皮下、网膜脂肪脂联素mRNA表达依次降低（P均＜0.01）.三组TG、LDL-C、FFA、FINS 和HOMA-IR比较均有统计学差异（P均＜0.01）.GDM组网膜脂肪脂联素mRNA表达与CRP、FPG、FINS、HOMA-IR和孕前BMI等呈负相关（P＜0.01或＜0.05）.结论 GDM患者的网膜脂肪脂联素mRNA表达降低与其IR及GDM发生有关.     

脂联素与2型糖尿病

脂联素是脂肪细胞分泌的蛋白质，具有重要的代谢作用，它在人体血液中的浓度为5～30μg／ml，在肥胖、胰岛素抵抗和2型糖尿病(T2DM)患者血浆脂联素浓度降低。葡萄糖胰岛素钳夹实验发现，脂联素水平与胰岛素作用的糖代谢呈正相关。脂联素基因在人类染色体上定位于3q27，这一位点恰恰是糖尿病的敏感位点。脂联素基因突变和低血浆脂联     

脂联素受体及其与2型糖尿病的关系

人脂联素受体AdipoR1和AdipoR2均在骨骼肌丰富表达。且两者的表达呈正相关。而小鼠AdipoR1主要在骨骼肌中表达,AdipoR2则主要在肝脏表达。AdipoR1／R2的表达还受到多种因素的调节,包括胰岛素、生长激素等。此外,AdipoR1／R2在胰岛素抵抗、2型糖尿病的发生、发展中扮演了重要的角色。对脂联素受体研究的逐步深入,将加深对脂联素作用机制的了解,从而有助于2型糖尿病的预防和治疗。     

脂联素与2型糖尿病及其大血管病变

脂联素与肥胖、胰岛素抵抗、2型糖尿病及其大血管病变的发生、发展有密切关系，被认为是一种保护性因子。本文从多方面就脂联素与2型糖尿病及其大血病变的关系加以总结。脂联素具有胰岛素抵抗及拮抗动脉粥样硬化的作用，对脂联素在2型糖尿病及其大血管病变方面的基础及临床研究，为改善胰岛素抵抗和防治2型糖尿病大血管病变提供了新的思路。     

肥胖和2型糖尿病患者脂肪组织脂联素mRNA表达的研究

用实时定量PCR技术检测2型糖尿病患者(肥胖与非肥胖)和非2型糖尿病者皮下及大网膜脂联素mRNA表达量;ELISA法测血清脂联素浓度。皮下脂肪脂联素mRNA表达量高于大网膜;2型糖尿病、肥胖患者大网膜脂肪脂联素mRNA表达量对血清脂联素浓度有影响;性别可影响脂联索mRNA表达。     

2型糖尿病患者血清脂联素水平与胰岛素抵抗的相关性

对58例2型糖尿病(T2DM)患者及30例健康者进行血清脂联秉(APN)、空腹血糖(FPG)、空腹胰岛素(FINS)测定,分析APN与胰岛素抵抗(IR)的相关性.结果 显示,T2DM患者血清APN明显低于健康者(P<0.01);血清APN与体质量指数、FPG、FINs、胰岛素抵抗指数均呈负相关(P<0.05,<0.01).提示T2DM患者血清APN水平明显降低,低脂联素血症与IR密切相关.     

2型糖尿病患者血清脂联素与肝脏脂肪含量的相关性研究

目的 探讨2型糖尿病患者血清脂联素水平与肝脏脂肪含量及相关临床指标的相关性.方法 选取天津市第三中心医院收治的初发2型糖尿病患者108例,以患者肝脏脂肪含量测定结果的平均数为切点将其分为2型糖尿病伴低肝脏脂肪含量组(T2DM+ LFC组)50例和2型糖尿病伴高肝脏脂肪含量组(T2DM+ HFC组)58例.应用高效液相层析法、葡萄糖氧化酶法、放射免疫法以及ELISA等分别对两组患者的相关临床指标及血清脂联素水平进行检测.采用t检验或X2检验进行组间对比,采用Spearman相关分析和多元逐步回归分析进行指标间关系判定,采用Logistic回归分析影响肝脏脂肪含量的危险因素.结果 T2DM+ HFC组血清脂联素水平显著低于T2DM+ LFC组(t=3.947,P=0.006).2型糖尿病患者血清脂联素水平与体重、体重指数、体脂含量、内脏脂肪面积、肝脏脂肪含量、甘油三酯水平呈显著负相关(r=-0.680 ～-0.225,P＜0.05或0.01).多元逐步回归分析显示,体重、体重指数和体脂含量是血清脂联素水平的独立相关因素.Logistic回归分析显示,体重(OR=1.288,95％ CI:1.009 ～ 1.644)、脂联素(OR=0.169,95％ CI:0.053 ～0.542)、γ-谷氨酰胺转肽酶(OR=1.155,95％ CI:1.032～ 1.293)及甘油三酯(OR=0.323,95％ CI:0.172～0.609)为2型糖尿病患者肝脏脂肪含量的影响因素.结论 血清脂联素水平与体重、体重指数和体脂含量密切相关,并可能在2型糖尿病患者肝脏脂质沉积过程中发挥重要调节作用.     

脂联素和胰岛素抵抗、2型糖尿病研究进展

研究证实脂联素(APN)有胰岛素增敏作用，能拮抗胰岛素抵抗。血浆APN的降低是发生胰岛素抵抗和糖尿病的独立危险因素。APN的胰岛素增敏作用是通过增加骨骼肌脂肪酸氧化以及抑制肝糖异生实现的。另外，APN基因多态性可引起APN生成和分泌的减少，也是导致胰岛素抵抗和糖尿病的原因之一。对APN的研究将为探讨胰岛素抵抗和2型糖尿病的发病机制及治疗方案提供新的线索。     

2型糖尿病及其大血管病变患者血清脂联素水平的研究

目的 探讨血清脂联素(ADP)水平及相关代谢指标与2型糖尿病(T2DM)及其大血管病变的相关性.方法 将80例2型糖尿病患者根据有无大血管病变分为无大血管病变组(30例)和伴大血管病变组(50例),并选取50例健康体检者作为对照组.检测空腹血糖(FPG)、血脂、C反应蛋白(CLRP)及血清脂联素等生化指标.酶联免疫法测定血清脂联素浓度,放射免疫法测定空腹胰岛素(FINS)浓度.计算稳态模式胰岛素抵抗指数(HOMA-IR).结果 T2DM组脂联素水平与对照组比较降低(P＜0.01);T2DM伴大血管病变组脂联素水平显著低于单纯T2DM组(P＜0.01).相关分析显示,脂联素与FPG、FINS、HOMA-IR及收缩压(SBP)呈负相关.多元逐步回归分析显示,脂联素与三酰甘油(TG)、FPG、CRP及HOMA-IR密切相关.结论 2型糖尿病及其伴大血管病变患者血清脂联素水平降低,脂联素可能延缓糖尿病及其大血管并发症的发生、发展,动态检测ADP水平对及早发现糖尿病大血管病变有临床意义.     

Tom-1基因在糖尿病胰岛素抵抗患者网膜脂肪组织表达定量研究

目的探讨Tom-1基因在2型糖尿病胰岛素抵抗(T2DM-IR)患者网膜脂肪组织表达水平。方法取T2DM-IR患者与非糖尿病无IR者(对照组)网膜脂肪组织,用荧光定量RT-PCR技术测定Tom-1 mRNA的表达量。结果Tom-1 mRNA的表达量在T2DM-IR组为4440±617拷贝/百万看家基因,对照组为1360±82拷贝/百万看家基因,两者比较差异有统计学意义(P<0.05)。结论在人腹腔网膜脂肪组织中Tom-1 mRNA有表达,在T2DM-IR组呈上调表达。因此,这条基因可能与T2DM的IR有关。     

脂联素mRNA在肥胖症患者腹部皮下与网膜脂肪组织中表达水平的研究

目的探讨肥胖症患者腹部皮下脂肪组织与大网膜脂肪组织脂联素的表达水平及与BMI、WHR、血脂、胰岛素敏感性的关系。方法用半定量RT-PCR方法检测19例肥胖症患者(BMI≥25·0kg/m2)和28例非肥胖症患者(BMI<25·0kg/m2)腹部皮下与大网膜脂肪组织脂联素mRNA的表达水平,并测量BMI、WHR、BP,FPG、FIns、血脂和胰岛素抵抗指数(HOMA-IR)。结果(1)肥胖组大网膜脂肪组织脂联素mRNA表达水平显著低于非肥胖组(P<0·05),肥胖组大网膜脂肪组织脂联素mRNA水平显著低于皮下脂肪组织(P<0·05)。(2)肥胖组FIns、HOMA-IR、BP、TG与VLDL-C均高于非肥胖组(P<0·05~P<0·01)。(3)非肥胖组中网膜脂肪组织脂联素mRNA表达量与BMI(r=-0·513,P<0·05)、VLDL-C(r=-0·733,P<0·01)显著负相关。结论肥胖症患者网膜脂肪组织脂联素mRNA表达水平显著降低,它可能在肥胖相关的代谢综合征的发病中起一定作用。     

Decreased expression of apM1 in omental and subcutaneous adipose tissue of humans with type 2 diabetes

We have screened a subtracted cDNA library in order to identify differentially expressed genes in omental adipose tissue of human patients with Type 2 diabetes. One clone (#1738) showed a marked reduction in omental adipose tissue from patients with Type 2 diabetes. Sequencing and BLAST analysis revealed clone #1738 was the adipocyte-specific secreted protein gene apM1 (synonyms ACRP30, AdipoQ, GBP28). Consistent with the murine orthologue, apM1 mRNA was expressed in cultured human adipocytes and not in preadipocytes. Using RT-PCR we confirmed that apM1 mRNA levels were significantly reduced in omental adipose tissue of obese patients with Type 2 diabetes compared with lean and obese normoglycemic subjects. Although less pronounced, apM1 mRNA levels were reduced in subcutaneous adipose tissue of Type 2 diabetic patients. Whereas the biological function of apM1 is presently unknown, the tissue specific expression, structural similarities to TNFalpha, and the dysregulated expression observed in obese Type 2 diabetic patients suggest that this factor may play a role in the pathogenesis of insulin resistance and Type 2 diabetes.     

SIRT1 mRNA在新诊断的2型糖尿病患者脂肪组织的表达及意义

目的探讨新诊断的2型糖尿病（T2DM）患者脂肪组织SIRT1 mRNA表达水平及其与体质指数（BMI）、腰臀比（WHR）、血糖、血浆胰岛素、胰岛素抵抗指数（HOMA—IR）关系。方法采用RT—PCR方法检测了40例对照组和40例T2DM患者脂肪组织SIRT1 mRNA水平,并分析了SIRT1水平与BMI、WHR、血脂、HbA1C、血糖、血浆胰岛素和HOMA—IR等的关系。结果新诊断的T2DM患者SIRT1 mRNA水平显著低于对照组（1．49±0．47VS1．12±0．32,P〈0．01）;线性相关分析表明,SIRT1与Fins、HOMA—IR呈显著负相关（r=-0．421,P〈0．01和r=-0．511,P〈0．01）。以SIRT1为因变量,年龄、WHR、BMI、TG、TC、LDL—C、HDL—C、HbA1C、FPG、Fins和HOMA—IR为自变量,进行多元线性逐步回归分析,结果表明HOMA—IR是影响SIRT1的独立相关因素。Logistic回归分析表明控制性别、年龄、WHR、BMI、TC、TG、HDL—C、LDL—C后,发现SIRT1与T2DM发病呈负相关,OR〈1。结论脂肪组织中SIRT1 mRNA水平的变化与IR和T2DM相关。     

Human subcutaneous adipose tissue Glut 4 mRNA expression in obesity and type 2 diabetes

Cellular resistance to insulin caused by reduced glucose transport and metabolism is a primary defect leading to the development of metabolic disease. While the etiology of insulin resistance is multifactorial, reduced insulin action is associated with impaired activity of the glucose transporter GLUT4 in insulin-sensitive tissues. Yet, the role of adipose tissue GLUT4 deregulation in the pathogenesis of insulin resistance, obesity, and diabetes is still unclear. In this study, we assessed the relative GLUT4 level in human subcutaneous adipose tissue from obese, diabetic, and diabetic obese versus control subjects, using a real-time PCR method. GLUT4 mRNA levels were considerably decreased among type 2 diabetic patients compared with those of the controls (P < 0.01), whereas no such difference was found between obese and normal-weight controls. Multiple linear regressions analysis in both diabetic non-obese and diabetic obese groups showed a negative correlation between GLUT4 mRNA expression and both markers of obesity or insulin resistance (P < 0.01). However, in obese group, GLUT4 was inversely associated only with HOMA-IR (P < 0.01). Our findings showed that adipose GLUT4 gene expression changes were more related to insulin resistance and type 2 diabetes rather than to obesity.     

Exercise training increases adipose tissue GLUT4 expression in patients with type 2 diabetes

We investigated the effects of exercise training on adipose tissue and skeletal muscle GLUT4 expression in patients with type 2 diabetes (T2D). Muscle and adipose tissue samples were obtained before and after 4-weeks of exercise training in seven patients with T2D [47 ± 2 years, body mass index (BMI) 28 ± 2]. Seven control subjects (54 ± 4, BMI 30 ± 2) were recruited for baseline comparison. Adipose tissue GLUT4 protein expression was 43% lower (p < 0.05) in patients with T2D compared with control subjects and exercise training increased (p < 0.05) adipose tissue GLUT4 expression by 36%. Skeletal muscle GLUT4 protein expression was not different between control subjects and patients with T2D. Exercise training increased (p < 0.05) skeletal muscle GLUT4 protein expression by 20%. In conclusion, 4-weeks of exercise training increased GLUT4 expression in adipose tissue and skeletal muscle of patients with T2D, although the functional benefits of this adaptation appear to be dependent on an optimal β-cell function.     

Genome-wide scan of resistin mRNA expression in omental adipose tissue of baboons

INTRODUCTION: The hormone resistin was recently discovered in adipose tissue of mice. Functional tests suggest a role for resistin in the regulation of insulin sensitivity. However, human studies have reported controversial results on the metabolic function of this hormone. METHODS: A 1 g omental adipose tissue biopsy was obtained from 404 adult baboons. Resistin mRNA expression was assayed by real-time, quantitative RT-PCR, and univariate and bivariate quantitative genetic analyses were performed, via the variance decomposition approach. A genome scan analysis was conducted using resistin mRNA abundance in omental adipose tissue as a quantitative phenotype. RESULTS: A significant heritability of h2 = 0.23 (P = 0.003) was found for resistin mRNA abundance in omental adipose tissue. A genome scan detected a quantitative trait locus for resistin expression with an LOD score of 3.8, in the region between markers D19S431 and D19S714, corresponding to human chromosome 19 p13. This chromosomal region contains genes related to insulin resistance phenotypes, such as resistin, insulin receptor, angiopoietin-like 4 protein and LDL receptor. CONCLUSIONS: Individual variation in resistin mRNA expression has a significant genetic component, and a gene or genes on chromosome 19 p13 may regulate resistin mRNA levels in baboon omental adipose tissue.     

2型糖尿病患者内脂素在网膜脂肪组织中的表达及与血清浓度的关系

目的探讨内脂素基因在2型糖尿病患者网膜脂肪组织中的表达情况及其与血清浓度的关系。方法选取2型糖尿病患者及健康对照者各60例,用Northern b lot印迹技术检测两组网膜脂肪组织内脂素mRNA的表达水平,并测定血浆内脂素浓度、空腹血糖、OGTT 2 h血糖、空腹胰岛素、血脂及其他生化指标。结果 2型糖尿病组网膜组织的内脂素mRNA表达显著高于对照组（P〈0.01）。两组网膜组织中内脂素mRNA表达与内脂素血清浓度呈正相关。结论 T2DM患者网膜内脂素mRNA表达量较对照组升高,且与血清浓度呈正相关。