脂联素及受体变化在妊娠期糖尿病发病中的意义和相关因素分析
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摘要
研究背景与目的
妊娠期糖尿病(gestational diabetes mellitus,GDM)是妊娠期发生或首次识别出的不同程度的葡萄糖耐量异常,严重危及母婴健康并与多种不良妊娠结局密切相关。GDM是2型糖尿病(type 2 diabetes,T2DM)的高危因素,尽早诊断并治疗GDM不仅可减少围产期母婴死亡率,并可能减少孕妇将来T2DM的发生。
GDM的发病机制与胰岛素抵抗(insulin resistance,IR)和胰岛功能减退有关。严重胰岛素抵抗的发生提示GDM患者与T2DM有共同发病机制。近年来参与其中的脂肪细胞因子及炎症因子成为新的研究热点。脂联素是脂肪细胞分泌的一种细胞因子,具有抗炎、抗糖尿病、抗动脉粥样硬化和增强胰岛素敏感性的作用。T2DM患者脂联素水平降低。以往脂联素与胰岛素抵抗机制关系的研究多集中于T2DM患者,对GDM的研究甚少。研究还显示T2DM患者血中游离脂肪酸(free fatty acid,FFA)升高,是一个独立的危险因素,而升高的FFA可导致胰岛素抵抗和胰岛β细胞的凋亡。此外,对T2DM的病因与发病机制的研究中,近年来炎症学说备受关注,低度炎症反应在T2DM的发病机制中扮演着重要角色。炎症因子C反应蛋白(C reactive protein,CRP)已被证实是T2DM事件的预测因子。作为T2DM高危因素的GDM,GDM患者血脂联素与FFA、CRP、IR关系如何,其网膜和皮下脂肪组织中的脂联素的表达如何,骨骼肌脂联素受体1有何变化,他们与IR有关因素的相关性如何,是否与2型糖尿病有类似的改变?这些问题鲜见研究。本研究以GDM为研究对象,设正常妊娠及非妊娠正常血糖组为对照1)观察脂联素、CRP及FFA等在GDM患者血中的变化,探讨其与IR及GDM发病的关系。2)用RT-PCR方法检测腹部皮下脂肪和大网膜脂肪脂联素mRNA、腹直肌脂联素受体1mRNA的表达水平,并比较它们与多种指标的关系,探讨GDM脂肪组织中的脂联素mRNA及腹直肌脂联素受体1mRNA表达水平变化与GDM IR和发病机制的关系。
材料与方法
受试对象经75克葡萄糖耐量试验后分为3组:①妊娠期糖尿病组(GDM组)②正常妊娠组(normal glucose tolerance,NGT)③非妊娠正常血糖对照组(normal control,NC)。方法(1)用ELISA法检测妊娠38周—40周GDM组、NGT、NC组血脂联素,同时检测FFA和CRP、空腹胰岛素、C肽,总胆固醇(total cholesterol,TC)、甘油三脂(triglyceride,TG)、高密度脂蛋白(high-density lipoprotein cholesterol,HDL-C)、低密度脂蛋白(low density lipoprotein cholesterol,LDL-C),测量身高、体重,计算体质指数(BMI)=体重(kg)/身高~2(m~2),采用稳态模型法(Homeostasis modelassessment,HOMA)评价胰岛素抵抗指数和胰岛β细胞功能即HOMA-IR=FINS×FPG/22.5;HOMA-β=ln[20×FINS/(FPG-3.5)]。通过统计分析,揭示血脂联素与各项指标之间的相互关系。(2)GDM组、NGT组剖腹产时、非妊娠正常血糖对照组(NC)手术时,患者知情同意的情况下在手术过程中取腹部皮下脂肪、大网膜脂肪及腹直肌组织标本,用于RNA提取。RT-PCR方法检测皮下脂肪和大网膜脂肪脂联素mRNA、腹直肌脂联素受体1 mRNA的表达水平。
结果
(1)各组血中测定指标比较①从NC组、NGT组到GDM组血脂联素水平逐渐降低,各组间差异有显著性(均P＜0.05);FFA水平逐渐升高,各组间差异有显著性;CRP逐渐升高,GDM组与NGT组和NC组间差异有显著性,而NGT组和NC组差异没有显著性。②GDM组血脂联素水平与HOMA-IR呈负相关关系(r=-0.560,P＜0.01),FFA与HOMA-IR呈正相关关系(r=0.515,P＜0.01),CRP水平与HOMA-IR呈正相关关系(r=0.640,P＜0.01)。③GDM组中以HOMA-IR为因变量的多元逐步回归分析显示,CRP、孕前BMI和脂联素最后进入方程,成为影响HOMA-IR最显著的因素。以脂联素为因变量的逐步多元回归分析显示,CRP和孕前BMI最后进入方程,成为影响脂联素最显著的因素。(2)剖腹产(GDM组、NGT组)及非孕手术对照组(NC组)①各组皮下、网膜脂肪组织脂联素mRNA表达量、各组腹直肌组织脂联素受体1 mRNA表达量从NC组、NGT组到GDM组逐渐降低,各组间差异有显著性(P＜0.01,P＜0.05);网膜脂肪组织脂联素mRNA表达量下降较皮下脂肪组织更明显。②GDM组中皮下脂肪组织脂联素mRNA表达量与HOMA-β、LDL-C呈正相关;网膜脂肪组织脂联素mRNA表达量与FPG、FINS、HOMA-IR呈负相关性,与HOMA-β呈正相关性;腹直肌组织脂联素受体1mRNA表达量与FPG、HOMA-IR、TC、TG负相关。
结论
(1)GDM患者存在严重的IR,;血脂联素、CRP和孕前BMI与IR独立相关;胰岛素抵抗参与GDM的发生。
(2)相对于正常妊娠组,GDM组CRP水平显著升高,FFA水平显著升高,提示慢性炎症反应和脂代谢紊乱与严重IR及GDM的发病有关。GDM组的血脂联素水平显著降低,且与HOMA-IR负相关,提示脂联素降低与严重IR及GDM的发病有关。
(3)GDM患者腹壁皮下、网膜脂肪组织脂联素mRNA水平均明显低于健康孕妇组及正常对照组;网膜脂肪组织脂联素mRNA水平下降更明显,提示其改变与GDM发生有关。
(4)GDM组网膜脂肪组织脂联素mRNA表达量与FPG、FINS、HOMA-IR呈负相关,网膜脂肪组织脂联素mRNA表达量与胰岛素抵抗有关,GDM呈现与2型糖尿病一致的改变。
(5)GDM组骨骼肌组织脂联素受体1 mRNA表达量低于健康孕妇组及正常对照组,各组间差异有显著性(P＜0.05)。GDM脂联素受体1mRNA表达量下降与糖脂代谢异常、IR密切相关。GDM血脂联素、皮下、网膜脂肪组织脂联素mRNA表达量下降,同时骨骼肌脂联素R1基因表达下调,进一步导致了脂联素不能有效结合受体,形成恶性循环。
Backgrouds and objectives
Gestational diabetes mellitus(GDM),a form of glucose intolerance which occurred during pregnancy,could do great harm to the health of pregnant women and fetus,and has been known for being closely correlated with poor outcomes of gestation.GDM is a risk factor for the later development of type 2 diabetes,and timely intervention to GDM may not only significantly decrease the mortality rate of fetus during perinatal period,but delay the onset of type 2 diabetes in women.Both insulin resistance and beta cell dysfunction have been thought being involved into the pathogenesis of GDM,while chronic insulin resistance share common mechanism in GDM and type 2 diabetes.Previous studies have found that C-reactive protein(CRP) and IL-6 are the predictors for type 2 diabetes, however whether cytokines could predict the onset of GDM or play an critical role in the progression of GDM still is unknown.
Free fatty acids(FFA) is the critical factor in the metabolism of lipid.It has been reported that elevated level of plasma FFA in type 2 diabetes subjects is an independent risk factor,and could lead to insulin resistance and increased apoptosis rate of beta cells,which may be conducted by the inflammation.Adiopnectin,one of the most important adipokines, is believed to possess the bioactivity like anti-inflammation,anti-diabetes,anti-artherosclerosis and improve insulin sensitivity.Not surprisingly,the level of plasma adiponectin was decreased in the type 2 diabetes patients.The studies concerning the association between GDM and adiponectin are few,though many have been done in the fields of its involvement in type 2 diabetes.
In the present study,80 subjects were stratified into three groups according to the fasting and 2h blood glucose:GDM group,normal glucose tolerance with gestation group and normal glucose.tolerance without gestation group.The expression level of adiponectin and its receptor in subcutaneous/abdominal fat and muscle was compared in these groups, so did other cytokines and FFA.Furthermore,the association between adiponectin and its receptor and insulin resistance in GDM was also assessed in this study.The measurements of serum CRP,adiponectin and FFA were then performed in these subjects,and the expression level of adiponectin and its receptor was detected in subcutaneous fat, abdominal fat and muscle tissues from these groups by using RT-PCR.
Subjects and methods
Based on the results of 75g oral glucose tolerance test,90 subjects were stratified into three groups according to the fasting and 2h blood glucose:GDM group,normal glucose tolerance with gestation group and normal glucose tolerance without gestation group. Anthropometric measurements included:height,weight,body mass index(BMI,kg/m~2). Blood samples for measurements of free fatty acid(FFA) and C peptide,total cholesterol (TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol (HDL-C),triglyceride(TG) and CRP levels were collected after an overnight fast.Plasma glucose was assayed by an automated glucose oxidase method.Insulin was determined by RIA.The concentration of serum adiponectin was measured by ELISA method.The homeostasis model(HOMA) model was adopted to calculate the index of insulin resistance HOMA-IR=FINS×FPG/22.5) and beta cell function(HOMA-β=20×FINS/(FPG-3.5)).
The expression level of adiponectin and its receptor was detected in subcutaneous fat, abdominal fat and muscle tissues from these groups by using RT-PCR.The study was designed in compliance with the ethics regulations set out by the Helsinki Declaration,and all subjects were well informed about the study before the consent was acquired.
Results
1.During the period between 38-40 weeks after gestation,
①The level of adiponectin was gradually decreased from NC group,NGT group to GDM group,and the difference between among these groups was significant(P＜0.05);The level of FFA was gradually increased from NC group,NGT group to GDM group,and the difference among these groups also was significant(P＜0.05);The level of CRP in GDM group was higher than those of NGT and NC group respectively(P＜0.05).
②In GDM group,the plasma level of adiponectin was negatively correlated with HOMA-IR(r=-0.560,P＜0.01),while the plasma level of FFA and CRP was positively correlated with HOMA-IR respectively(r=0.515,P＜0.01;r=0.640,P＜0.01);
③Stepwise regression analysis indicated that CRP,BMI(before gestation) and adiponectin was the last ones enter the equations,when HOMA-IR was taken as dependent variable.While in the stepwise regression analysis,in which adiponectin was taken as dependent variable,CRP and weight entered the equations last.
2.During the period from38-40 weeks after gestation,
①The mRNA expression of adiponectin and its receptor in subcutaneous and abdominal fat was gradually decreased from NC group to GDM group(P＜0.05).
②In GDM group,the mRNA expression of adiponectin in subcutaneous adipose tissue was positively correlated with HOMA-β,and the level of LDL-C;the mRNA expression of adiponectin in abdominal adipose tissue was negatively correlated with FPG, FINS and HOMA-IR;the mRNA expression of adiponectin receptor was negatively correlated with FPG,HOMA-IR,TC and TG.
Conclusions
(1) GDM subjects has increased insulin resistance,and CRP,BMI(before gestation) and plasma adiponectin was independently associated with IR,which demonstrated that the insulin resistance was involved in the onset of GDM.
(2) The level of CRP and FFA was higher in GDM than that of gestation group with normal glucose tolerance,which suggested the chronic inflammation was associated with lipidemia and insulin resistance.The level of plasma adiponectin was significantly decreased in GDM,and negatively correlated with HOMA-IR,which indicated that the adiponectin played an role in the insulin resistance and the onset of GDM.
(3) The level of mRNA expression of adiponectin in subcutaneous adipose tissue was significantly decreased in GDM subjects than those of gestation group and normal control, while the abdominal tissue decreased even more,indicating its role in GDM.
(4) The mRNA expression of adiponectin in abdominal adipose tissue in GDM was negatively correlated with FPG,FINS and HOMA-IR,which suggest that the adiponectin in abdominal adipose tissue is involved in the development of insulin resistance.
(5)The level of mRNA expression of adiponectin receptor 1 in muscle tissue was lower than that in normal gestation group and control group.(P＜0.05),which means this decrease was closely correlated with glucolipid metabolism and insulin resistance.
妊娠期糖尿病(gestational diabetes mellitus,GDM)是妊娠期发生或首次识别出的不同程度的葡萄糖耐量异常,严重危及母婴健康并与多种不良妊娠结局密切相关。GDM是2型糖尿病(type 2 diabetes,T2DM)的高危因素,尽早诊断并治疗GDM不仅可减少围产期母婴死亡率,并可能减少孕妇将来T2DM的发生。
GDM的发病机制与胰岛素抵抗(insulin resistance,IR)和胰岛功能减退有关。严重胰岛素抵抗的发生提示GDM患者与T2DM有共同发病机制。近年来参与其中的脂肪细胞因子及炎症因子成为新的研究热点。脂联素是脂肪细胞分泌的一种细胞因子,具有抗炎、抗糖尿病、抗动脉粥样硬化和增强胰岛素敏感性的作用。T2DM患者脂联素水平降低。以往脂联素与胰岛素抵抗机制关系的研究多集中于T2DM患者,对GDM的研究甚少。研究还显示T2DM患者血中游离脂肪酸(free fatty acid,FFA)升高,是一个独立的危险因素,而升高的FFA可导致胰岛素抵抗和胰岛β细胞的凋亡。此外,对T2DM的病因与发病机制的研究中,近年来炎症学说备受关注,低度炎症反应在T2DM的发病机制中扮演着重要角色。炎症因子C反应蛋白(C reactive protein,CRP)已被证实是T2DM事件的预测因子。作为T2DM高危因素的GDM,GDM患者血脂联素与FFA、CRP、IR关系如何,其网膜和皮下脂肪组织中的脂联素的表达如何,骨骼肌脂联素受体1有何变化,他们与IR有关因素的相关性如何,是否与2型糖尿病有类似的改变?这些问题鲜见研究。本研究以GDM为研究对象,设正常妊娠及非妊娠正常血糖组为对照1)观察脂联素、CRP及FFA等在GDM患者血中的变化,探讨其与IR及GDM发病的关系。2)用RT-PCR方法检测腹部皮下脂肪和大网膜脂肪脂联素mRNA、腹直肌脂联素受体1mRNA的表达水平,并比较它们与多种指标的关系,探讨GDM脂肪组织中的脂联素mRNA及腹直肌脂联素受体1mRNA表达水平变化与GDM IR和发病机制的关系。
材料与方法
受试对象经75克葡萄糖耐量试验后分为3组:①妊娠期糖尿病组(GDM组)②正常妊娠组(normal glucose tolerance,NGT)③非妊娠正常血糖对照组(normal control,NC)。方法(1)用ELISA法检测妊娠38周—40周GDM组、NGT、NC组血脂联素,同时检测FFA和CRP、空腹胰岛素、C肽,总胆固醇(total cholesterol,TC)、甘油三脂(triglyceride,TG)、高密度脂蛋白(high-density lipoprotein cholesterol,HDL-C)、低密度脂蛋白(low density lipoprotein cholesterol,LDL-C),测量身高、体重,计算体质指数(BMI)=体重(kg)/身高~2(m~2),采用稳态模型法(Homeostasis modelassessment,HOMA)评价胰岛素抵抗指数和胰岛β细胞功能即HOMA-IR=FINS×FPG/22.5;HOMA-β=ln[20×FINS/(FPG-3.5)]。通过统计分析,揭示血脂联素与各项指标之间的相互关系。(2)GDM组、NGT组剖腹产时、非妊娠正常血糖对照组(NC)手术时,患者知情同意的情况下在手术过程中取腹部皮下脂肪、大网膜脂肪及腹直肌组织标本,用于RNA提取。RT-PCR方法检测皮下脂肪和大网膜脂肪脂联素mRNA、腹直肌脂联素受体1 mRNA的表达水平。
结果
(1)各组血中测定指标比较①从NC组、NGT组到GDM组血脂联素水平逐渐降低,各组间差异有显著性(均P＜0.05);FFA水平逐渐升高,各组间差异有显著性;CRP逐渐升高,GDM组与NGT组和NC组间差异有显著性,而NGT组和NC组差异没有显著性。②GDM组血脂联素水平与HOMA-IR呈负相关关系(r=-0.560,P＜0.01),FFA与HOMA-IR呈正相关关系(r=0.515,P＜0.01),CRP水平与HOMA-IR呈正相关关系(r=0.640,P＜0.01)。③GDM组中以HOMA-IR为因变量的多元逐步回归分析显示,CRP、孕前BMI和脂联素最后进入方程,成为影响HOMA-IR最显著的因素。以脂联素为因变量的逐步多元回归分析显示,CRP和孕前BMI最后进入方程,成为影响脂联素最显著的因素。(2)剖腹产(GDM组、NGT组)及非孕手术对照组(NC组)①各组皮下、网膜脂肪组织脂联素mRNA表达量、各组腹直肌组织脂联素受体1 mRNA表达量从NC组、NGT组到GDM组逐渐降低,各组间差异有显著性(P＜0.01,P＜0.05);网膜脂肪组织脂联素mRNA表达量下降较皮下脂肪组织更明显。②GDM组中皮下脂肪组织脂联素mRNA表达量与HOMA-β、LDL-C呈正相关;网膜脂肪组织脂联素mRNA表达量与FPG、FINS、HOMA-IR呈负相关性,与HOMA-β呈正相关性;腹直肌组织脂联素受体1mRNA表达量与FPG、HOMA-IR、TC、TG负相关。
结论
(1)GDM患者存在严重的IR,;血脂联素、CRP和孕前BMI与IR独立相关;胰岛素抵抗参与GDM的发生。
(2)相对于正常妊娠组,GDM组CRP水平显著升高,FFA水平显著升高,提示慢性炎症反应和脂代谢紊乱与严重IR及GDM的发病有关。GDM组的血脂联素水平显著降低,且与HOMA-IR负相关,提示脂联素降低与严重IR及GDM的发病有关。
(3)GDM患者腹壁皮下、网膜脂肪组织脂联素mRNA水平均明显低于健康孕妇组及正常对照组;网膜脂肪组织脂联素mRNA水平下降更明显,提示其改变与GDM发生有关。
(4)GDM组网膜脂肪组织脂联素mRNA表达量与FPG、FINS、HOMA-IR呈负相关,网膜脂肪组织脂联素mRNA表达量与胰岛素抵抗有关,GDM呈现与2型糖尿病一致的改变。
(5)GDM组骨骼肌组织脂联素受体1 mRNA表达量低于健康孕妇组及正常对照组,各组间差异有显著性(P＜0.05)。GDM脂联素受体1mRNA表达量下降与糖脂代谢异常、IR密切相关。GDM血脂联素、皮下、网膜脂肪组织脂联素mRNA表达量下降,同时骨骼肌脂联素R1基因表达下调,进一步导致了脂联素不能有效结合受体,形成恶性循环。
Backgrouds and objectives
Gestational diabetes mellitus(GDM),a form of glucose intolerance which occurred during pregnancy,could do great harm to the health of pregnant women and fetus,and has been known for being closely correlated with poor outcomes of gestation.GDM is a risk factor for the later development of type 2 diabetes,and timely intervention to GDM may not only significantly decrease the mortality rate of fetus during perinatal period,but delay the onset of type 2 diabetes in women.Both insulin resistance and beta cell dysfunction have been thought being involved into the pathogenesis of GDM,while chronic insulin resistance share common mechanism in GDM and type 2 diabetes.Previous studies have found that C-reactive protein(CRP) and IL-6 are the predictors for type 2 diabetes, however whether cytokines could predict the onset of GDM or play an critical role in the progression of GDM still is unknown.
Free fatty acids(FFA) is the critical factor in the metabolism of lipid.It has been reported that elevated level of plasma FFA in type 2 diabetes subjects is an independent risk factor,and could lead to insulin resistance and increased apoptosis rate of beta cells,which may be conducted by the inflammation.Adiopnectin,one of the most important adipokines, is believed to possess the bioactivity like anti-inflammation,anti-diabetes,anti-artherosclerosis and improve insulin sensitivity.Not surprisingly,the level of plasma adiponectin was decreased in the type 2 diabetes patients.The studies concerning the association between GDM and adiponectin are few,though many have been done in the fields of its involvement in type 2 diabetes.
In the present study,80 subjects were stratified into three groups according to the fasting and 2h blood glucose:GDM group,normal glucose tolerance with gestation group and normal glucose.tolerance without gestation group.The expression level of adiponectin and its receptor in subcutaneous/abdominal fat and muscle was compared in these groups, so did other cytokines and FFA.Furthermore,the association between adiponectin and its receptor and insulin resistance in GDM was also assessed in this study.The measurements of serum CRP,adiponectin and FFA were then performed in these subjects,and the expression level of adiponectin and its receptor was detected in subcutaneous fat, abdominal fat and muscle tissues from these groups by using RT-PCR.
Subjects and methods
Based on the results of 75g oral glucose tolerance test,90 subjects were stratified into three groups according to the fasting and 2h blood glucose:GDM group,normal glucose tolerance with gestation group and normal glucose tolerance without gestation group. Anthropometric measurements included:height,weight,body mass index(BMI,kg/m~2). Blood samples for measurements of free fatty acid(FFA) and C peptide,total cholesterol (TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol (HDL-C),triglyceride(TG) and CRP levels were collected after an overnight fast.Plasma glucose was assayed by an automated glucose oxidase method.Insulin was determined by RIA.The concentration of serum adiponectin was measured by ELISA method.The homeostasis model(HOMA) model was adopted to calculate the index of insulin resistance HOMA-IR=FINS×FPG/22.5) and beta cell function(HOMA-β=20×FINS/(FPG-3.5)).
The expression level of adiponectin and its receptor was detected in subcutaneous fat, abdominal fat and muscle tissues from these groups by using RT-PCR.The study was designed in compliance with the ethics regulations set out by the Helsinki Declaration,and all subjects were well informed about the study before the consent was acquired.
Results
1.During the period between 38-40 weeks after gestation,
①The level of adiponectin was gradually decreased from NC group,NGT group to GDM group,and the difference between among these groups was significant(P＜0.05);The level of FFA was gradually increased from NC group,NGT group to GDM group,and the difference among these groups also was significant(P＜0.05);The level of CRP in GDM group was higher than those of NGT and NC group respectively(P＜0.05).
②In GDM group,the plasma level of adiponectin was negatively correlated with HOMA-IR(r=-0.560,P＜0.01),while the plasma level of FFA and CRP was positively correlated with HOMA-IR respectively(r=0.515,P＜0.01;r=0.640,P＜0.01);
③Stepwise regression analysis indicated that CRP,BMI(before gestation) and adiponectin was the last ones enter the equations,when HOMA-IR was taken as dependent variable.While in the stepwise regression analysis,in which adiponectin was taken as dependent variable,CRP and weight entered the equations last.
2.During the period from38-40 weeks after gestation,
①The mRNA expression of adiponectin and its receptor in subcutaneous and abdominal fat was gradually decreased from NC group to GDM group(P＜0.05).
②In GDM group,the mRNA expression of adiponectin in subcutaneous adipose tissue was positively correlated with HOMA-β,and the level of LDL-C;the mRNA expression of adiponectin in abdominal adipose tissue was negatively correlated with FPG, FINS and HOMA-IR;the mRNA expression of adiponectin receptor was negatively correlated with FPG,HOMA-IR,TC and TG.
Conclusions
(1) GDM subjects has increased insulin resistance,and CRP,BMI(before gestation) and plasma adiponectin was independently associated with IR,which demonstrated that the insulin resistance was involved in the onset of GDM.
(2) The level of CRP and FFA was higher in GDM than that of gestation group with normal glucose tolerance,which suggested the chronic inflammation was associated with lipidemia and insulin resistance.The level of plasma adiponectin was significantly decreased in GDM,and negatively correlated with HOMA-IR,which indicated that the adiponectin played an role in the insulin resistance and the onset of GDM.
(3) The level of mRNA expression of adiponectin in subcutaneous adipose tissue was significantly decreased in GDM subjects than those of gestation group and normal control, while the abdominal tissue decreased even more,indicating its role in GDM.
(4) The mRNA expression of adiponectin in abdominal adipose tissue in GDM was negatively correlated with FPG,FINS and HOMA-IR,which suggest that the adiponectin in abdominal adipose tissue is involved in the development of insulin resistance.
(5)The level of mRNA expression of adiponectin receptor 1 in muscle tissue was lower than that in normal gestation group and control group.(P＜0.05),which means this decrease was closely correlated with glucolipid metabolism and insulin resistance.
引文
1 Buchanan TA,Xiang A,Kjos SL,Lee WP,Trigo E,Nader I,Bergner EA,PalmerJP,Peters RK.Gestational diabetes:antepartum characteristics that predict postpartum glucose Intolerance and type 2 diabetes in Latino women.Diabetes 1998 Aug;47(8):1302-10.
2 Hotta K,Funahashi T,Arita Y,et al.Plasma concentrations of a novel adipose-specific protein,adiponectin,in type 2 diabetic patients[J].Arterioscler Thromb Vasc Biol,2000,20(6):1595.1599.
3 Carlsson M,Wessman Y,Almgren P.et al.High levels of nonesterified fatty acids are associated with increased familial risk of caridiovascular disease.Arterioscler Throm Vasc Biol,2000,20;1588-1594.
4 扬治芳,毛季萍,汤佳珍.2型糖尿病患者游离脂肪酸与大血管病变的相关性研究.中华糖尿病杂志,2004,12,12,100-103.
5 Burt RL,Peripheral utilization of glucose in pregnancy.Ill.insulin tolerance.Obstet Gynecol.1956;2:658-665.
6 Mulford MI,Jovanonic-peterson CM.Alternative therapies for the management of Gestational diabetes.Clin Perintol,1993;20:619-634.
7 Stanley K,Fraser R,Bruce C.Physiological changes in insulin resistance in human pregnancy:longitudinal study with the hyperinsulinaemic euglycaemic clamp technique.Br J Obstet Gynaecol.1998;105(7):756-9.
8 Yamashita,H,Jianhua,S,and Friedman,J.E.Physiologic and molecular alterations in carbohydrate metabolism during pregnancy and gestational diabetes mellitus.J.Clin.Obst.Gyn.2000.43:87-98
9 Catalano PM,Roman-Drago NM,Amini SB,Sims EA.Longitudinal changes in Body composition and energy balance in lean women with normal and abnormal glucose tolerance during pregnancy.Am J Obstet Gynecol.19981;179(1):156-65.
10 Xiang AM,Peters RK,Trigo E,Kjos SL,Lee WP,Buchanan TA.Multiple metabolic defects during late pregnancy in women at high risk for type 2 Diabetes. Diabetes.1999;48(4):848-54.
11 Skouby SO,Kuhl C,Honnes PJ,Andersen AN,Prolactin and glucose tolerance in Normal and gestational diabetic pregnancy.Obstet Gynecol,1986;67:17-20.
12 Kirwan JP,Hauguel-De Mouzon S,Lepercq J,Challier JC,Huston-Presley L,Friedman JE,Kalhan SC,Catalano PM.TNF-alpha is a predictor of insulin Resistance in human pregnancy.Diabetes,2002,51(7):2207-13.
13 Anila V,Charlotte M,Boney,et al.Insulin Resistance Syndrome in Women with Prior History of Gestational Diabetes Mellitys.J Clin Endocrinol Metab,2002,87(7):3227-35.
14 Ryan EA,Osullivan MJ,Skuler JS,et al.Insulin action during pregnancy:Studies with the euglucemic clamp technique[J].Diabetes,1985,34:380-389.
15 Barbour.LA.New concepts in insulin resistance of pregnancy and gestational diabetes:long-term implications for mother and offspring,Am J Obstet Gynecol,2003.23(5):545-549.
16 16.26.Lindsay RS,Funahashi T,Hanson RL,et al.Adiponectin and development of type 2 diabetes in the Prima lndian population.Lancet,2002,360:57-58.
17 Park KG,Park KS,Kim MJ,et al.Relationship beween serum adiponectin and leptin concentrations and body fat distribution.Diabetes Res Clin Pract,2004,63(2);135-142.
18 Weyer C,Funahashi T,Tanaka S.Hypoadiponectinem ia in obesity and type 2 diabetes:close association with insulin resistance and hyperinsuliem ia.J Clin Endocrinol Metab,2001;86(5):1930.
19 庄向华,董砚虎,许爱梅,等.糖尿病一级亲属脂联素和瘦素与胰岛素抵抗的相关性.中华糖尿病杂志,2005,13(1):8210.
20 Yang WS,Lee WJ,Funahashi T.Weight reduction increases plasma levels of an adipose-derived anti-inflammatory Protein adiponectin.J Clin Endocrinol Metab,2001;86(8):3815
21 Beltowski J.Adiponectin and resistin-new hormones of white adipose tissue[J].Med sci Monit,20039(2):RA55-RA62.
22 Yamauchi T,Kamon J,Minokosh IY,et al.Adiponectin stimulates glucose utilization and fatty - acidoxidation by activating AMP- activated p rotein kinase [J]. Nature Med, 2002,8( 11 ):1288 -1295.
23 Myles W, Karen H, Laura S, etal. First-trimester c-reactive protein and subsequent gestational diabetes[J]. DiabetesCare,2003,26:819-24.
24 Leipold H, WordaC, Gruber C J, etal.Gestational diabetes mellitus is associated with increased C-reactive Protein concentration in the third but not second trimester[J].Eur J Clin lnvest,2005,35(12):752-7
25 Winzer C, Wagner O, Festa A, etal. Plasma adiponectin, Insulin sensitivity and sub-clinical inflamation in women with Priorgestational diabetes mellitus [J].Diabetes Care, 2004,27(7):1721-7.
26 Carlsson M,Wessman Y,Almgren P.etal.High levels of nonesterified fatty acids are associated with increased familial risk of caridiovascular disease.Arterioscler Throm Vasc Biol,2000,20;1588-1594.
27 Randle PJ, Garland PB, Hales CN, et al. The glucose fatty acid cycle:its role in insulin sensitivity and metabbolic disturbance of diabetes melitus. Lancet, 1963,1: 785-789.
28 Schulze M B, Rimm E B, Shai I, et al. Relationship betweenadiponectin and glycemic control, blood lipids, and inflammatory markers in men with type 2 diabetes[J]. Diabetes Care,2004,27:1680-1687.
1 Hotmnisligil GS. Molecular mechanisms of insulin resistance and the role of the adipo -cyte [J].Int J Obes Relat Metab Disord,2000,24 (supple4):s23-s24
2 Yatagai T,Nagasaka S,Taniguchi A,et al.Hypoadiponectinmia is associated with visceral fat accumulation and insulin resistance in Japanese men with type2 diabetes mellitus.Metabolism,2003,52:1274-1278.
3 Takahashi M,Arita Y,Yamagata K,et al.Genomic structure and mutations inadipose specific gene,adiponectin.Int J Obes,2000,24:861-8683.
4 Motoshima H,Wu X,Sinha MK,et al.Differential regulation of adiponectin secretion from cultured humanomental and subcutaneous adipocytes:effects of insulin and rosiglitazone[J].J Clin Endocrinol Metab,2002,87(12):5662-5667
5 Cseh K, Baranyi E,Nelezer Z, et ah Plasma adiponectin and pregnancy induced insulin resistance[ J]. Diabetes Care, 2003, 26 (8): 2244-2249.
6 Williams M A, Qiu C, Muy-Rivera M, et al Plasma adiponectin concentrations in early pregnancy and subsequent risk of gestational diabetesmellitus[ J]. J Clin Endocrinol Metab, 2004, 89 (5): 2306-2311.
7 Winzer C, Wagner O, Fwata A, et ah Plasma adiponectin, insulin sensitivity, and subclinical inflammation in women with priorgestational DM [J] .Diabetes Care, 2004, 27(7): 1721-1727.
8 Altomonte J,Harbaran S,Richter A,et al.Fat depot-specific expression of adiponectin is impaired in Zucker fatty rats [J]. Metabolism, 2003; 52:958-963
9 Kern PA,Di Gregorio GB,Lu T,et al.Adiponectin expression from human adipose tissue:relation to obesity,insulin resistance,and tumor necrosis factor-alpha expression [J].Diabetes,2003,52(7):1779-1785.
10 Fisher,F M,McTernan P G,Valsamakis G, et al.Differences in adiponectin protein expression:effect of fat depots and type 2 diabetic status[J].Horm Metab Res,2002, 34(11-12):650-654
11 Motoshima H,Wu X,Sinha MK,et al.Differential regulation of adiponectin secretion from cultured human omental and subcutaneous adipocytes:effects of insulin and rosiglitazone[J].J Clin Endocrinol Metab,2002,87 (12):5662-5667
12 Philip KG, Gregorio D,Lu T,et al.Adiponectin expression from human adipose tissue:relation to obesity,insulin resistance and tumor necrosis-a expression. Diabetes, 2003,52:1779-1785.
13 Halleux C M, Tahashi M, Delporte M L,et al. Secretion of adiponectin and regulation of apM1 gene expression inhuman visceral adipose tissue [J]. Biochem Biophys Res Commun, 2001, 288:1102-1 107
14 Combs T P, Wagner J A, Berger J, et al. Induction of adipocyte complement related protein of 30 kilodaltons by PPAR-gamma agonists: a potential mechanism of insulin sensitization[J]. Endocrinology, 2002,143:998 -1007
15 Maeda N, Takahashi M, Funahashi T, et al. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose derived protein[J]. Diabetes, 2001, 50:2094-2099
16 Yu J G, Javorschi S, Hevener A L, et al. The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects[J]. Diabetes, 2002,51:2968-2974
17 Phillips S A, Ciaraldi T P, Kong A P, et al. Modulation of circulating and adipose tissue adiponectin levels by antidiabetic therapy [J]. Diabetes, 2003, 52:667-674
18 Retnakaran R, Hanley A.J.G, Raif N,etal .Adiponectin and beta cell dysfunction in gestational diabetes: Pathophysiological implications. Diabeteologta, 2005, 48: 993-1001
19 Yamauchi T, Kamon J ,Ito Y ,et al.Cloning adiponectin receptors That mediate antidiabetic metabolic effects[J].Nature,2003,423 (6941): 762-769.
20 Wang J, Hug C , Amad N S,et al .T- cadherinis receptor for hexameric And high-molecular-weight forms Acrp30/adiponectin[J].PN AS , 2004 , 101 (28): 10308-10313
21 Civitarese A E, Jenkinson C P,Richardson D ,et al .Adiponectin Receptors gene expression and insulin sensitivity in non-diabetic Mexican Americans with or without a family history of Type2 diabetes [J] .Diabetologia, 2004,47(5 ):816-820.
22 Staiger H ,Kaltenbach S ,Staiger K ,et al. Expression adiponectin receptor mRNA in humans keletal muscle cells is related to in vivo paramers glucose and lipid metabolism (J). Diabetes,2003,53 (9 )2195 -2201.
23 Tsuchida A ,Yamauchi T ,Ito Y ,et al.Insulin/Foxol pathway regulates Expression levels of adiponectin receptors and adiponectin sensi- tivity.J Biol Chem, 2004, 279: 30817 -30822.
24 Inukai K ,Nakashima Y ,Watanabe M ,et al .Regulation of adiponectin receptor gene expression in diabetic mice[J].Am J Physiol Endocrinol Metab , 2005 , 288(5): 876-882.
25 Yamauclu T ,Kanan J ,Ito Y ,et al .Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature,2003,423:762-769.
26 Yao H,Ling H ,Wang H ,et al.Gene expression of adiponectin and Adiponectin receptor 1 in type2 diabetic rats and the relationship with the parameters of glucose and lipid metabolism. J Huazhong Univ Sci Technolog Med Sci,2005,25:285-288.
27 Tsuchida A, Yamauchi T, Ito Y, et al. Insulin/Foxol Pathway RegulatesExpression Levels of Adiponectin Receptors and Adiponectin Sensitivity. J Biol Chem, 2004,279(29): 30817-30822
28 Liu Y ,Wan Q ,Guan Q ,et al.High-fat diet feeding impairs both the Expression and activity of AMPKa in rats' skeletal muscle.Bio chem. Bio phys Res Commun. 2006,339(2):701-7
29 Stefan N, Vozarova B, Funahashi T, etal. Plasma adiponectin concentration is associated tyrosine phosphorylation and with low skeletal muscle insulin receptor plasma concentration precedes a de cr eas ei nw holebodyi nsulins ensitivityi nh umans.Diabetes, 2002,51(6 ) :1 884-1888
30 Michael LF, Wu Z, CheathamRB, et al. Restoration of insulin-sensitive glucose trans -porter ( GLUT4) gene expression in muscle cells by the transcription alcoactivator PGC 1.Prac Natl Acad Sci USA,2001, 98(7) :3820-3825
31 Tsuchida A,Y amauchiT , Ito Y ,et al.Insulin/Foxol Pathway Regulates Expression Levels of Adiponectin Receptors and Adiponectin Sensitivity.) Biol Chem,2004,279 (29): 30817-30822
1 Cypryk K, Pertynska- Marczewska M, Szymczak W,et al. Overweight and obesity as common risk factors for gestational diabetes mellitus GDM, perinatal macrosomy in offspring and Type -2 diabetes mothers.(J) Przegl Lek. 2005, 62(1):38-41
2 Claus K .Etiology and pathogenesis of gestational diabetes.Di abetes Care. 1998, 21 (Supp12): 19-26.
3 Persson B ,Edwall L ,Hanson U ,et al.Insulin sensitivity and Insulin response in Woman with gestational diabetes mellitus. Horm Metab Res.1997,29:393-397.
4 Burt RL, Peripheral utilization of glucose in pregnancy.Ill.insulin tolerance. Obstet Gynecol. 1956;2 :658-665.
5 Mulford MI, Jovanonic-peterson CM. Alternative therapies for the management of Gestational diabetes. Clin Perintol,1993;20:619-634
6 Stanley K, Fraser R, Bruce C. Physiological changes in insulin resistance in human pregnancy: longitudinal study with the hyperinsulinaemic euglycaemic clamp technique. Br J Obstet Gynaecol.1998; 105(7):756-9.
7 Yamashita, H, Jianhua, S, and Friedman, J.E. Physiologic and molecular alterations in carbohydrate metabolism during pregnancy and gestational diabetes mellitus.J .Clin. Obst. Gyn.2000.43:87-98
8 Ryan EA, O 'Sulliban MJ, Skyler JS .Insulin action during pregnancy:Studies with the euglycemic clamp technique.Diabetes.1985;34:380-389.
9 Okereke NC, Huston-Presley L , Amini SB, Kalhan S ,Catalano PM. Longitudinal changes in energy expenditure and body composition in obese women with normal and impaired glucose tolerance Am J Physiol Endocrinol Metab.2004; 287(3):E472-9.
10 Catalano PM, Roman-Drago NM, Amini SB, Sims EA. Longitudinal changes in Body composition and energy balance in lean women with normal and abnormal glucose tolerance during pregnancy. Am J Obstet Gynecol .19981;179(1):156-65.
11 Akbay E, Tiras MB, Yetkin 1, Toruner F, Ersoy R, Uysal S, Ayvaz G. Insulin secretion and insulin sensitivity in normal pregnancy and gestational diabetes mellitus.Gynecol Endocrinol. 2003; 17(2): 137-142.
12 英豪,王德芬.孕晚期妊娠期糖尿病胰岛素抵抗和分泌关系的探讨.现代妇产科进展,2002;11(1):42-44
13 Xiang AM,Peters RK,Trigo E,Kjos SL,Lee WP,Buchanan TA.Multiple metabolic defects during late pregnancy in women at high risk for type 2 Diabetes.Diabetes.1999;48(4):848-54.
14 Skouby SO,Kuhl C,Honnes PJ,Andersen AN,Prolactin and glucose tolerance in Normal and gestational diabetic pregnancy.Obstet Gynecol,1986;67:17-20.
15 Kirwan JP,Hauguel-De Mouzon S,Lepercq J,Challier JC,Huston-Presley L,Friedman JE,Kalhan SC,Catalano PM.TNF-alpha is a predictor of insulin Resistance in human pregnancy.Diabetes,2002,51(7):2207-13.
16 Catalano PM,Kirwan JP,de Mouzon SH,King J.Gestational diabetes and insulin resistance:role in short-and long-term implications for mother and fetus.J Nutr.2003;133:1674s-1683s
17 Yamauchi T,Kamon J,Waki H,et al.The fat-derived hor-mone adiponectin reverses insulin resistance associated withboth lipoatrophy and obesity[J].Nat Med,2001,7:941-946
18 Takahashi M,Arita Y,Yamagata K,et al.Genomic structured and mutations inadipose-specific gene,adiponectin[J].Int J obes Relal Metab Disord,2000,24:861-868
19 Hara K,Boutin P,Mori Y,et al.Genetic variation in thegene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population[J].Diabetes,2002,51:536-540
20 Kondo H,Shimomura I,Matsukawa Y,et al.Associationof adiponectin mutation with type 2 Diabetes[J].Diabetes,2002,51:2 325-2 328
21 Harvest F Gu,Adili Abulaiti,Claes-Goran Ostenson,et al.Single nucleotide polymorphisms in the proximal promoterregion of the adiponectin(APM1) gene are associated withtype 2 diabetes in Swedish Caucasians[J].Diabetes,2004,53:31-36
22 Halleux CM,Tahashi M,Delporte ML,et al.Secretion ofadiponectin and regulation of apM1 gene expression inhuman visceral adipose tissue[J].Biochem Biophys ResCommun,2001,288:1 102-1 107
23 Combs TP, Wagner JA, Berger J, et al. Induction of adipocyte complement-related protein of 30 kilodaltons by PPAR-gamma agonists: a potential mechanism of insulin sensitization[J]. Endocrinology, 2002,143:998-1 007
24 Maeda N, Takahashi M, Funahashi T, et al. PPARgamma ligands increase expression and plasma concentrations ofadiponectin, an adipose-derived protein[J]. Diabetes, 2001,50: 2094-2099
25 Yu JG, Javorschi S, Hevener AL, et al. The effect of thiazolidinediones on plasma adiponectin levels in normal,obese, and type 2 diabetic subjects[J]. Diabetes, 2002,51:2968-2974
26 Phillips SA, Ciaraldi TP, Kong AP, et al. Modulation of circulating and adipose tissue adiponectin levels by antidiabetic therapy[J]. Diabetes, 2003, 52:667-674
27 Stefan N, Vozarova B, Funahashi T, et al. Plasma adip-onectin concentration is associated with skeletal muscleinsulin receptor tyrosine phosphorylation, and low plasmaconcentration precedes a decrease in whole-body insulinsensitivity in humans[J]. Diabetes, 2002,51:1884-1888
28 Cnop M, Havel PJ, Utzschneider KM, et al. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex[J]. Diabetologia, 2003,46:459-469
29 Guldstrand M, Ahren B, Adamson U. Improved beta-cell function after standardized weight reduction in severely obese subjects[J]. Am J Physiol Endocrinol Metab, 2003,284:557-565
30 Ma K, Cabrero A, Sana PK, et al. Increased beta-oxidation but no insulin resistance or glucose intolerance in mice lacking adiponectin [J]. J Biol Chem, 2002, 277:34658-34661
31 Kumada M,Kihara S,Sumitsuji S,et al ·Association of hypoadiponectinemia with coronary artery disease inmen[J]·Arteriosclerosis Thromb Vasc Biol,2003,23(1):85-89.
32 Kawano T,Saito T,Yasu T,et al·Close association of hypoadiponectinemia with arteriosclerosis obliteransand ischemic heart disease[J]·Metabolism, 2005, 54(5):653-656.
33 Ishikawa Y,Akasaka Y,Ishii T,et al·Changes in the distribution pattern of gelatin- binding protein of 28 kDa(adiponectin) in myocardial remodeling after is-chaemic injury[J]·Histopathology,2003,42 (1): 43-52.
34 Zoccali C, Mallamaci F,Tripepi G,et al·Adiponectin, metabolic risk factors,and cardiovascular events amongpatients with end-stage renal disease[J]·J Am Soc Nephrol,2002,13(1):134-141.
35 Maeda N,Takahashi I,Funahashi T,et al·PPARgam-ma ligands increase expression and plasma concentrations of adiponectin,an adipose-derived protein [J]·Diabetes, 2001, 50(9): 2094-2099.
36 Ouchi N,Kihara S,Arita Y,et al·Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin[J]·Circulation,1999,100(25):2473-2476.
37 Yokota T,Oritani K,Takahashi I,et al·Adiponectin,a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages [J]· Blood,2000,96(5):1723-1732.
38 Hotta K,Funahashi T,Bodkin NL,et al·Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys[J]·Diabetes,2001,50(5):1126-1133.
39 Matsuda M,Shimomura I,Sata M,et al·Role of adiponectin in preventing vascular stenosis·The missin link of adipo-vascular axis[J]·J Biol Chem,2002,277
40 Ranheim T,Haugen F, StaffAC, et al. Adiponectin is reduced in gestational diabetes mellitus in normalweightwomen[ J]. Acta ObstetGynecolScand, 2004, 83(4): 341-347.
41 CsehK, BaranyiE,NelezerZ, etal. Plasma adiponectin and pregnancy induced insulin resistance[ J]. Diabetes Care, 2003, 26 (8): 2244-2249.
42 W illiamsMA, Qiu C,Muy-Rivera M, et al. Plasma adiponectin concentrations in early pregnancy and subsequent risk of gestational diabetesmellitus[ J]. J Clin EndocrinolMetab, 2004, 89 (5): 2306-2311.
43 W inzerC,WagnerO, FwataA, etal. Plasma adiponectin, insulin sensitivity, and subclinical inflammation inwomenwith priorgestational DM[J].DiabetesCare, 2004, 27(7): 1721-1727.
44 Zhang Y, Pmenen R, MoHei M, et al. Positional doning'the mouse obese gene and its human homologue[J].Natrue,l 994,372 ( 65 05 ) ;425-032.
45 MagniP ,I JuzaA ,D oss,E ,et a 1. Free and bound plasmal leptin in normal weight and obese men and women; relationship with body composition, resting energe expenditum, insuiln- sensitivity, lipid profile and macornutrient preference[J].Clin Endminol (Oxf), 2005 ,62(2); 189-196
46 Chiu K C, Chu A, Chusng L M, st al. Association of leptin receptor polymorphism with insulin resistance [J].Eur J Endoerinol, 2004,150(5):725-729.
47 Burguem B, Conce M E , longJ ,et al. the longform of the lepitn receptor( OB-Rb) is widely expressed in the human brain[ J ] .Neuroendocrinology,2 000,71(3): 187.
48 Zamboni M, Zoico E, Fantin F, et al. Relation between leptin and the metabolic syodrome in elderly- women [ J].Gerontol Biol Sci Med Sci, 2004,59(4):396-400.
49 Steinberger J ,Siefen L Jacobs D R Jr . Relation of leptin to insulin resistance syndrome in childern [J]Obes Res,2 003,11( 9):11 24 -11 30
50 Wanters M ,Considim R V,Yudkinl S . Lepitn levels in type2 diabetes: associations with measures of insulin resistance and insulin secretion. [J]. Horm Metab Res,2003, 35(2):92-96.
51 ValleM ,G aeeunF ,M anos R .Low-grade systemic inflamration hypoadiponectinemia and a high cocentration of leptin are present in very young obese children,and corelate with metabolic syndrome[ J]. Int J Obes Relat Metab Disord, 2003,27 (1):13-18.
52 Hennige A M ,Stefan N,K appK ,at al .Leptin down-regulates insulin action through phosphorylation of serine-318 in insulin receptor substrate 1 [J].FASEBJ , 2006 , 20(18):1206-1208.
53 Fruhbeck G, Salvador J. Relation between leptin and the regulation of glucose metabolism [ J].Diabetologia 2000,43(1);3-12
54 Pocai A, Morgan K, Buetner C,et al. Central leptin acutely reverses diet-induced hepatic inslin resisatnce [J].Diabetes,2 005,54(1 1) ;31 82 -31 89.
55 Ympelkis B B, Singh M K, Krisan A D, et al. Chronic leptin treatment enhances insulin sitmulated glucose disposal in skeletal muscle of high -fat fed rodens[1] .Life Sci,2004,74 (14); 1801-1816 .
56 Swceney G, Keen J, So-. R, et .High leptin level acutely inhibit insulin-simulated uptake without affecting glucose transportor 4 translocation in 16 rat skeletal muscle cells [J ]. Endocrinology, 2001,1 42(11);4 806-4812.
57 Qiu CA, Michele A, Wiiliams S, et al. Incresed maternal Plasama leptin in early pregnancy and rik of gastational diabetes mellitus.[J] .Obsetrics & Cynecology, 2004103:519-525.
58 Kylie AM, David ON, Alicia J, et al .Do adiponectin, TNFa, lepitn and CPR relate to insuiln resistance in pregnacny ?Studies in women with and wihtout gestational diabetes, during and after pregnancy [J].Diabetes Metab Res Rev, 2006, 22:131-138
59 westgate J A, Lindsay R S, Beattie J, et al .Hyperinsulinemia in cord blood in mothers with type2 diabetes and gestational diabetes meliltus in New Zealand (J) .Diabetes Care. 2006, 29(6): 1345-1350
60 Kinalski M, Sledzewski A, Kowalska 1, et al. Postpartum maternal plasmal leptin levels and their relationship to gestational diabetes mellitus ( J)Med wieku Rozwoj, 2004, 8:703-710,
61 Vitoratos N, Salamalekis E. Matermal plasma leptin levels and their relationship to insulin and glugose in gestation onset diabetes(J).Cynecol Obstet lnvest, 2001, 51(1):17-21.
62 Kim K H, Lee K,Moon YS, et al.Cystine-rich adipose tissue-specific secretory factor inhibits adipocyte differenciation (J). J Biol chem, 2001,276 (14):11252-11256.
63 Chosh S,Singh AK, Antna B,et al. The genomic organization of mouse resistin reveals major differences from the human resistin:functional implications[J]. Gene, 2003, 305(1):27-34.
64 Moore GB, Chapman H,Holder JC,et al. Differential regulation of adipocytokine mRNAs by rosiglitazone in db/db mice [J].Biocbem Biophys Res Commun, 2001,286(4):735-741
65 Way JM,Gorgun CZ, Tong Q, et al. Adipose tissue resistin expression is severely suppressed in obesity and stimulated by PPARr agonist [J] . J Biol Chem, 2001, 276(28):25651-25653
66 Steppan CM, Bailey ST, Bhat S, et al.The hormone resistin links obesity to diabetes[J].Nature,2001,409(6818):307-312.
67 Steppan CM,Brown EJ,Wright CM,el al,A family of tissue specific resistin like molecules[J].Proc Natl Acad Sci USA,2001,98(2):502-506
68 McTeman CL,McTeman PG,Herte AL,et al.Resistin,central obeisty and 2 diabetes [J].Lancet,2002,359(9300):46-48
69 王学晶,徐国宾,朱立华,健康人、单纯性肥胖、糖尿病和甲亢患者的血浆reisiti 水平研究[J].中华检验医学杂志,2001,24(6):359-362
70 张建梁,秦水文,郑兴,等.人血清抵抗素水平与体脂含量和血糖及血压的相关性研究[J].中华医学杂志,2002,8(23):1609-1612.
71 Rajah M W,Qi Y,Pa et al.Regulation of -Men aperssica and circulating levels in obesity,diabetes,and fastingtJ]—Diabetes,2004,53(7):1671-1679
72 周咏明,余美霞,薛克营,等.皮下脂肪和胎盘的抵抗素表达及与胰岛素抵抗的关系.中国实用内科杂志.2005,25(11):972-974
2 Hotta K,Funahashi T,Arita Y,et al.Plasma concentrations of a novel adipose-specific protein,adiponectin,in type 2 diabetic patients[J].Arterioscler Thromb Vasc Biol,2000,20(6):1595.1599.
3 Carlsson M,Wessman Y,Almgren P.et al.High levels of nonesterified fatty acids are associated with increased familial risk of caridiovascular disease.Arterioscler Throm Vasc Biol,2000,20;1588-1594.
4 扬治芳,毛季萍,汤佳珍.2型糖尿病患者游离脂肪酸与大血管病变的相关性研究.中华糖尿病杂志,2004,12,12,100-103.
5 Burt RL,Peripheral utilization of glucose in pregnancy.Ill.insulin tolerance.Obstet Gynecol.1956;2:658-665.
6 Mulford MI,Jovanonic-peterson CM.Alternative therapies for the management of Gestational diabetes.Clin Perintol,1993;20:619-634.
7 Stanley K,Fraser R,Bruce C.Physiological changes in insulin resistance in human pregnancy:longitudinal study with the hyperinsulinaemic euglycaemic clamp technique.Br J Obstet Gynaecol.1998;105(7):756-9.
8 Yamashita,H,Jianhua,S,and Friedman,J.E.Physiologic and molecular alterations in carbohydrate metabolism during pregnancy and gestational diabetes mellitus.J.Clin.Obst.Gyn.2000.43:87-98
9 Catalano PM,Roman-Drago NM,Amini SB,Sims EA.Longitudinal changes in Body composition and energy balance in lean women with normal and abnormal glucose tolerance during pregnancy.Am J Obstet Gynecol.19981;179(1):156-65.
10 Xiang AM,Peters RK,Trigo E,Kjos SL,Lee WP,Buchanan TA.Multiple metabolic defects during late pregnancy in women at high risk for type 2 Diabetes. Diabetes.1999;48(4):848-54.
11 Skouby SO,Kuhl C,Honnes PJ,Andersen AN,Prolactin and glucose tolerance in Normal and gestational diabetic pregnancy.Obstet Gynecol,1986;67:17-20.
12 Kirwan JP,Hauguel-De Mouzon S,Lepercq J,Challier JC,Huston-Presley L,Friedman JE,Kalhan SC,Catalano PM.TNF-alpha is a predictor of insulin Resistance in human pregnancy.Diabetes,2002,51(7):2207-13.
13 Anila V,Charlotte M,Boney,et al.Insulin Resistance Syndrome in Women with Prior History of Gestational Diabetes Mellitys.J Clin Endocrinol Metab,2002,87(7):3227-35.
14 Ryan EA,Osullivan MJ,Skuler JS,et al.Insulin action during pregnancy:Studies with the euglucemic clamp technique[J].Diabetes,1985,34:380-389.
15 Barbour.LA.New concepts in insulin resistance of pregnancy and gestational diabetes:long-term implications for mother and offspring,Am J Obstet Gynecol,2003.23(5):545-549.
16 16.26.Lindsay RS,Funahashi T,Hanson RL,et al.Adiponectin and development of type 2 diabetes in the Prima lndian population.Lancet,2002,360:57-58.
17 Park KG,Park KS,Kim MJ,et al.Relationship beween serum adiponectin and leptin concentrations and body fat distribution.Diabetes Res Clin Pract,2004,63(2);135-142.
18 Weyer C,Funahashi T,Tanaka S.Hypoadiponectinem ia in obesity and type 2 diabetes:close association with insulin resistance and hyperinsuliem ia.J Clin Endocrinol Metab,2001;86(5):1930.
19 庄向华,董砚虎,许爱梅,等.糖尿病一级亲属脂联素和瘦素与胰岛素抵抗的相关性.中华糖尿病杂志,2005,13(1):8210.
20 Yang WS,Lee WJ,Funahashi T.Weight reduction increases plasma levels of an adipose-derived anti-inflammatory Protein adiponectin.J Clin Endocrinol Metab,2001;86(8):3815
21 Beltowski J.Adiponectin and resistin-new hormones of white adipose tissue[J].Med sci Monit,20039(2):RA55-RA62.
22 Yamauchi T,Kamon J,Minokosh IY,et al.Adiponectin stimulates glucose utilization and fatty - acidoxidation by activating AMP- activated p rotein kinase [J]. Nature Med, 2002,8( 11 ):1288 -1295.
23 Myles W, Karen H, Laura S, etal. First-trimester c-reactive protein and subsequent gestational diabetes[J]. DiabetesCare,2003,26:819-24.
24 Leipold H, WordaC, Gruber C J, etal.Gestational diabetes mellitus is associated with increased C-reactive Protein concentration in the third but not second trimester[J].Eur J Clin lnvest,2005,35(12):752-7
25 Winzer C, Wagner O, Festa A, etal. Plasma adiponectin, Insulin sensitivity and sub-clinical inflamation in women with Priorgestational diabetes mellitus [J].Diabetes Care, 2004,27(7):1721-7.
26 Carlsson M,Wessman Y,Almgren P.etal.High levels of nonesterified fatty acids are associated with increased familial risk of caridiovascular disease.Arterioscler Throm Vasc Biol,2000,20;1588-1594.
27 Randle PJ, Garland PB, Hales CN, et al. The glucose fatty acid cycle:its role in insulin sensitivity and metabbolic disturbance of diabetes melitus. Lancet, 1963,1: 785-789.
28 Schulze M B, Rimm E B, Shai I, et al. Relationship betweenadiponectin and glycemic control, blood lipids, and inflammatory markers in men with type 2 diabetes[J]. Diabetes Care,2004,27:1680-1687.
1 Hotmnisligil GS. Molecular mechanisms of insulin resistance and the role of the adipo -cyte [J].Int J Obes Relat Metab Disord,2000,24 (supple4):s23-s24
2 Yatagai T,Nagasaka S,Taniguchi A,et al.Hypoadiponectinmia is associated with visceral fat accumulation and insulin resistance in Japanese men with type2 diabetes mellitus.Metabolism,2003,52:1274-1278.
3 Takahashi M,Arita Y,Yamagata K,et al.Genomic structure and mutations inadipose specific gene,adiponectin.Int J Obes,2000,24:861-8683.
4 Motoshima H,Wu X,Sinha MK,et al.Differential regulation of adiponectin secretion from cultured humanomental and subcutaneous adipocytes:effects of insulin and rosiglitazone[J].J Clin Endocrinol Metab,2002,87(12):5662-5667
5 Cseh K, Baranyi E,Nelezer Z, et ah Plasma adiponectin and pregnancy induced insulin resistance[ J]. Diabetes Care, 2003, 26 (8): 2244-2249.
6 Williams M A, Qiu C, Muy-Rivera M, et al Plasma adiponectin concentrations in early pregnancy and subsequent risk of gestational diabetesmellitus[ J]. J Clin Endocrinol Metab, 2004, 89 (5): 2306-2311.
7 Winzer C, Wagner O, Fwata A, et ah Plasma adiponectin, insulin sensitivity, and subclinical inflammation in women with priorgestational DM [J] .Diabetes Care, 2004, 27(7): 1721-1727.
8 Altomonte J,Harbaran S,Richter A,et al.Fat depot-specific expression of adiponectin is impaired in Zucker fatty rats [J]. Metabolism, 2003; 52:958-963
9 Kern PA,Di Gregorio GB,Lu T,et al.Adiponectin expression from human adipose tissue:relation to obesity,insulin resistance,and tumor necrosis factor-alpha expression [J].Diabetes,2003,52(7):1779-1785.
10 Fisher,F M,McTernan P G,Valsamakis G, et al.Differences in adiponectin protein expression:effect of fat depots and type 2 diabetic status[J].Horm Metab Res,2002, 34(11-12):650-654
11 Motoshima H,Wu X,Sinha MK,et al.Differential regulation of adiponectin secretion from cultured human omental and subcutaneous adipocytes:effects of insulin and rosiglitazone[J].J Clin Endocrinol Metab,2002,87 (12):5662-5667
12 Philip KG, Gregorio D,Lu T,et al.Adiponectin expression from human adipose tissue:relation to obesity,insulin resistance and tumor necrosis-a expression. Diabetes, 2003,52:1779-1785.
13 Halleux C M, Tahashi M, Delporte M L,et al. Secretion of adiponectin and regulation of apM1 gene expression inhuman visceral adipose tissue [J]. Biochem Biophys Res Commun, 2001, 288:1102-1 107
14 Combs T P, Wagner J A, Berger J, et al. Induction of adipocyte complement related protein of 30 kilodaltons by PPAR-gamma agonists: a potential mechanism of insulin sensitization[J]. Endocrinology, 2002,143:998 -1007
15 Maeda N, Takahashi M, Funahashi T, et al. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose derived protein[J]. Diabetes, 2001, 50:2094-2099
16 Yu J G, Javorschi S, Hevener A L, et al. The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects[J]. Diabetes, 2002,51:2968-2974
17 Phillips S A, Ciaraldi T P, Kong A P, et al. Modulation of circulating and adipose tissue adiponectin levels by antidiabetic therapy [J]. Diabetes, 2003, 52:667-674
18 Retnakaran R, Hanley A.J.G, Raif N,etal .Adiponectin and beta cell dysfunction in gestational diabetes: Pathophysiological implications. Diabeteologta, 2005, 48: 993-1001
19 Yamauchi T, Kamon J ,Ito Y ,et al.Cloning adiponectin receptors That mediate antidiabetic metabolic effects[J].Nature,2003,423 (6941): 762-769.
20 Wang J, Hug C , Amad N S,et al .T- cadherinis receptor for hexameric And high-molecular-weight forms Acrp30/adiponectin[J].PN AS , 2004 , 101 (28): 10308-10313
21 Civitarese A E, Jenkinson C P,Richardson D ,et al .Adiponectin Receptors gene expression and insulin sensitivity in non-diabetic Mexican Americans with or without a family history of Type2 diabetes [J] .Diabetologia, 2004,47(5 ):816-820.
22 Staiger H ,Kaltenbach S ,Staiger K ,et al. Expression adiponectin receptor mRNA in humans keletal muscle cells is related to in vivo paramers glucose and lipid metabolism (J). Diabetes,2003,53 (9 )2195 -2201.
23 Tsuchida A ,Yamauchi T ,Ito Y ,et al.Insulin/Foxol pathway regulates Expression levels of adiponectin receptors and adiponectin sensi- tivity.J Biol Chem, 2004, 279: 30817 -30822.
24 Inukai K ,Nakashima Y ,Watanabe M ,et al .Regulation of adiponectin receptor gene expression in diabetic mice[J].Am J Physiol Endocrinol Metab , 2005 , 288(5): 876-882.
25 Yamauclu T ,Kanan J ,Ito Y ,et al .Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature,2003,423:762-769.
26 Yao H,Ling H ,Wang H ,et al.Gene expression of adiponectin and Adiponectin receptor 1 in type2 diabetic rats and the relationship with the parameters of glucose and lipid metabolism. J Huazhong Univ Sci Technolog Med Sci,2005,25:285-288.
27 Tsuchida A, Yamauchi T, Ito Y, et al. Insulin/Foxol Pathway RegulatesExpression Levels of Adiponectin Receptors and Adiponectin Sensitivity. J Biol Chem, 2004,279(29): 30817-30822
28 Liu Y ,Wan Q ,Guan Q ,et al.High-fat diet feeding impairs both the Expression and activity of AMPKa in rats' skeletal muscle.Bio chem. Bio phys Res Commun. 2006,339(2):701-7
29 Stefan N, Vozarova B, Funahashi T, etal. Plasma adiponectin concentration is associated tyrosine phosphorylation and with low skeletal muscle insulin receptor plasma concentration precedes a de cr eas ei nw holebodyi nsulins ensitivityi nh umans.Diabetes, 2002,51(6 ) :1 884-1888
30 Michael LF, Wu Z, CheathamRB, et al. Restoration of insulin-sensitive glucose trans -porter ( GLUT4) gene expression in muscle cells by the transcription alcoactivator PGC 1.Prac Natl Acad Sci USA,2001, 98(7) :3820-3825
31 Tsuchida A,Y amauchiT , Ito Y ,et al.Insulin/Foxol Pathway Regulates Expression Levels of Adiponectin Receptors and Adiponectin Sensitivity.) Biol Chem,2004,279 (29): 30817-30822
1 Cypryk K, Pertynska- Marczewska M, Szymczak W,et al. Overweight and obesity as common risk factors for gestational diabetes mellitus GDM, perinatal macrosomy in offspring and Type -2 diabetes mothers.(J) Przegl Lek. 2005, 62(1):38-41
2 Claus K .Etiology and pathogenesis of gestational diabetes.Di abetes Care. 1998, 21 (Supp12): 19-26.
3 Persson B ,Edwall L ,Hanson U ,et al.Insulin sensitivity and Insulin response in Woman with gestational diabetes mellitus. Horm Metab Res.1997,29:393-397.
4 Burt RL, Peripheral utilization of glucose in pregnancy.Ill.insulin tolerance. Obstet Gynecol. 1956;2 :658-665.
5 Mulford MI, Jovanonic-peterson CM. Alternative therapies for the management of Gestational diabetes. Clin Perintol,1993;20:619-634
6 Stanley K, Fraser R, Bruce C. Physiological changes in insulin resistance in human pregnancy: longitudinal study with the hyperinsulinaemic euglycaemic clamp technique. Br J Obstet Gynaecol.1998; 105(7):756-9.
7 Yamashita, H, Jianhua, S, and Friedman, J.E. Physiologic and molecular alterations in carbohydrate metabolism during pregnancy and gestational diabetes mellitus.J .Clin. Obst. Gyn.2000.43:87-98
8 Ryan EA, O 'Sulliban MJ, Skyler JS .Insulin action during pregnancy:Studies with the euglycemic clamp technique.Diabetes.1985;34:380-389.
9 Okereke NC, Huston-Presley L , Amini SB, Kalhan S ,Catalano PM. Longitudinal changes in energy expenditure and body composition in obese women with normal and impaired glucose tolerance Am J Physiol Endocrinol Metab.2004; 287(3):E472-9.
10 Catalano PM, Roman-Drago NM, Amini SB, Sims EA. Longitudinal changes in Body composition and energy balance in lean women with normal and abnormal glucose tolerance during pregnancy. Am J Obstet Gynecol .19981;179(1):156-65.
11 Akbay E, Tiras MB, Yetkin 1, Toruner F, Ersoy R, Uysal S, Ayvaz G. Insulin secretion and insulin sensitivity in normal pregnancy and gestational diabetes mellitus.Gynecol Endocrinol. 2003; 17(2): 137-142.
12 英豪,王德芬.孕晚期妊娠期糖尿病胰岛素抵抗和分泌关系的探讨.现代妇产科进展,2002;11(1):42-44
13 Xiang AM,Peters RK,Trigo E,Kjos SL,Lee WP,Buchanan TA.Multiple metabolic defects during late pregnancy in women at high risk for type 2 Diabetes.Diabetes.1999;48(4):848-54.
14 Skouby SO,Kuhl C,Honnes PJ,Andersen AN,Prolactin and glucose tolerance in Normal and gestational diabetic pregnancy.Obstet Gynecol,1986;67:17-20.
15 Kirwan JP,Hauguel-De Mouzon S,Lepercq J,Challier JC,Huston-Presley L,Friedman JE,Kalhan SC,Catalano PM.TNF-alpha is a predictor of insulin Resistance in human pregnancy.Diabetes,2002,51(7):2207-13.
16 Catalano PM,Kirwan JP,de Mouzon SH,King J.Gestational diabetes and insulin resistance:role in short-and long-term implications for mother and fetus.J Nutr.2003;133:1674s-1683s
17 Yamauchi T,Kamon J,Waki H,et al.The fat-derived hor-mone adiponectin reverses insulin resistance associated withboth lipoatrophy and obesity[J].Nat Med,2001,7:941-946
18 Takahashi M,Arita Y,Yamagata K,et al.Genomic structured and mutations inadipose-specific gene,adiponectin[J].Int J obes Relal Metab Disord,2000,24:861-868
19 Hara K,Boutin P,Mori Y,et al.Genetic variation in thegene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population[J].Diabetes,2002,51:536-540
20 Kondo H,Shimomura I,Matsukawa Y,et al.Associationof adiponectin mutation with type 2 Diabetes[J].Diabetes,2002,51:2 325-2 328
21 Harvest F Gu,Adili Abulaiti,Claes-Goran Ostenson,et al.Single nucleotide polymorphisms in the proximal promoterregion of the adiponectin(APM1) gene are associated withtype 2 diabetes in Swedish Caucasians[J].Diabetes,2004,53:31-36
22 Halleux CM,Tahashi M,Delporte ML,et al.Secretion ofadiponectin and regulation of apM1 gene expression inhuman visceral adipose tissue[J].Biochem Biophys ResCommun,2001,288:1 102-1 107
23 Combs TP, Wagner JA, Berger J, et al. Induction of adipocyte complement-related protein of 30 kilodaltons by PPAR-gamma agonists: a potential mechanism of insulin sensitization[J]. Endocrinology, 2002,143:998-1 007
24 Maeda N, Takahashi M, Funahashi T, et al. PPARgamma ligands increase expression and plasma concentrations ofadiponectin, an adipose-derived protein[J]. Diabetes, 2001,50: 2094-2099
25 Yu JG, Javorschi S, Hevener AL, et al. The effect of thiazolidinediones on plasma adiponectin levels in normal,obese, and type 2 diabetic subjects[J]. Diabetes, 2002,51:2968-2974
26 Phillips SA, Ciaraldi TP, Kong AP, et al. Modulation of circulating and adipose tissue adiponectin levels by antidiabetic therapy[J]. Diabetes, 2003, 52:667-674
27 Stefan N, Vozarova B, Funahashi T, et al. Plasma adip-onectin concentration is associated with skeletal muscleinsulin receptor tyrosine phosphorylation, and low plasmaconcentration precedes a decrease in whole-body insulinsensitivity in humans[J]. Diabetes, 2002,51:1884-1888
28 Cnop M, Havel PJ, Utzschneider KM, et al. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex[J]. Diabetologia, 2003,46:459-469
29 Guldstrand M, Ahren B, Adamson U. Improved beta-cell function after standardized weight reduction in severely obese subjects[J]. Am J Physiol Endocrinol Metab, 2003,284:557-565
30 Ma K, Cabrero A, Sana PK, et al. Increased beta-oxidation but no insulin resistance or glucose intolerance in mice lacking adiponectin [J]. J Biol Chem, 2002, 277:34658-34661
31 Kumada M,Kihara S,Sumitsuji S,et al ·Association of hypoadiponectinemia with coronary artery disease inmen[J]·Arteriosclerosis Thromb Vasc Biol,2003,23(1):85-89.
32 Kawano T,Saito T,Yasu T,et al·Close association of hypoadiponectinemia with arteriosclerosis obliteransand ischemic heart disease[J]·Metabolism, 2005, 54(5):653-656.
33 Ishikawa Y,Akasaka Y,Ishii T,et al·Changes in the distribution pattern of gelatin- binding protein of 28 kDa(adiponectin) in myocardial remodeling after is-chaemic injury[J]·Histopathology,2003,42 (1): 43-52.
34 Zoccali C, Mallamaci F,Tripepi G,et al·Adiponectin, metabolic risk factors,and cardiovascular events amongpatients with end-stage renal disease[J]·J Am Soc Nephrol,2002,13(1):134-141.
35 Maeda N,Takahashi I,Funahashi T,et al·PPARgam-ma ligands increase expression and plasma concentrations of adiponectin,an adipose-derived protein [J]·Diabetes, 2001, 50(9): 2094-2099.
36 Ouchi N,Kihara S,Arita Y,et al·Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin[J]·Circulation,1999,100(25):2473-2476.
37 Yokota T,Oritani K,Takahashi I,et al·Adiponectin,a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages [J]· Blood,2000,96(5):1723-1732.
38 Hotta K,Funahashi T,Bodkin NL,et al·Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys[J]·Diabetes,2001,50(5):1126-1133.
39 Matsuda M,Shimomura I,Sata M,et al·Role of adiponectin in preventing vascular stenosis·The missin link of adipo-vascular axis[J]·J Biol Chem,2002,277
40 Ranheim T,Haugen F, StaffAC, et al. Adiponectin is reduced in gestational diabetes mellitus in normalweightwomen[ J]. Acta ObstetGynecolScand, 2004, 83(4): 341-347.
41 CsehK, BaranyiE,NelezerZ, etal. Plasma adiponectin and pregnancy induced insulin resistance[ J]. Diabetes Care, 2003, 26 (8): 2244-2249.
42 W illiamsMA, Qiu C,Muy-Rivera M, et al. Plasma adiponectin concentrations in early pregnancy and subsequent risk of gestational diabetesmellitus[ J]. J Clin EndocrinolMetab, 2004, 89 (5): 2306-2311.
43 W inzerC,WagnerO, FwataA, etal. Plasma adiponectin, insulin sensitivity, and subclinical inflammation inwomenwith priorgestational DM[J].DiabetesCare, 2004, 27(7): 1721-1727.
44 Zhang Y, Pmenen R, MoHei M, et al. Positional doning'the mouse obese gene and its human homologue[J].Natrue,l 994,372 ( 65 05 ) ;425-032.
45 MagniP ,I JuzaA ,D oss,E ,et a 1. Free and bound plasmal leptin in normal weight and obese men and women; relationship with body composition, resting energe expenditum, insuiln- sensitivity, lipid profile and macornutrient preference[J].Clin Endminol (Oxf), 2005 ,62(2); 189-196
46 Chiu K C, Chu A, Chusng L M, st al. Association of leptin receptor polymorphism with insulin resistance [J].Eur J Endoerinol, 2004,150(5):725-729.
47 Burguem B, Conce M E , longJ ,et al. the longform of the lepitn receptor( OB-Rb) is widely expressed in the human brain[ J ] .Neuroendocrinology,2 000,71(3): 187.
48 Zamboni M, Zoico E, Fantin F, et al. Relation between leptin and the metabolic syodrome in elderly- women [ J].Gerontol Biol Sci Med Sci, 2004,59(4):396-400.
49 Steinberger J ,Siefen L Jacobs D R Jr . Relation of leptin to insulin resistance syndrome in childern [J]Obes Res,2 003,11( 9):11 24 -11 30
50 Wanters M ,Considim R V,Yudkinl S . Lepitn levels in type2 diabetes: associations with measures of insulin resistance and insulin secretion. [J]. Horm Metab Res,2003, 35(2):92-96.
51 ValleM ,G aeeunF ,M anos R .Low-grade systemic inflamration hypoadiponectinemia and a high cocentration of leptin are present in very young obese children,and corelate with metabolic syndrome[ J]. Int J Obes Relat Metab Disord, 2003,27 (1):13-18.
52 Hennige A M ,Stefan N,K appK ,at al .Leptin down-regulates insulin action through phosphorylation of serine-318 in insulin receptor substrate 1 [J].FASEBJ , 2006 , 20(18):1206-1208.
53 Fruhbeck G, Salvador J. Relation between leptin and the regulation of glucose metabolism [ J].Diabetologia 2000,43(1);3-12
54 Pocai A, Morgan K, Buetner C,et al. Central leptin acutely reverses diet-induced hepatic inslin resisatnce [J].Diabetes,2 005,54(1 1) ;31 82 -31 89.
55 Ympelkis B B, Singh M K, Krisan A D, et al. Chronic leptin treatment enhances insulin sitmulated glucose disposal in skeletal muscle of high -fat fed rodens[1] .Life Sci,2004,74 (14); 1801-1816 .
56 Swceney G, Keen J, So-. R, et .High leptin level acutely inhibit insulin-simulated uptake without affecting glucose transportor 4 translocation in 16 rat skeletal muscle cells [J ]. Endocrinology, 2001,1 42(11);4 806-4812.
57 Qiu CA, Michele A, Wiiliams S, et al. Incresed maternal Plasama leptin in early pregnancy and rik of gastational diabetes mellitus.[J] .Obsetrics & Cynecology, 2004103:519-525.
58 Kylie AM, David ON, Alicia J, et al .Do adiponectin, TNFa, lepitn and CPR relate to insuiln resistance in pregnacny ?Studies in women with and wihtout gestational diabetes, during and after pregnancy [J].Diabetes Metab Res Rev, 2006, 22:131-138
59 westgate J A, Lindsay R S, Beattie J, et al .Hyperinsulinemia in cord blood in mothers with type2 diabetes and gestational diabetes meliltus in New Zealand (J) .Diabetes Care. 2006, 29(6): 1345-1350
60 Kinalski M, Sledzewski A, Kowalska 1, et al. Postpartum maternal plasmal leptin levels and their relationship to gestational diabetes mellitus ( J)Med wieku Rozwoj, 2004, 8:703-710,
61 Vitoratos N, Salamalekis E. Matermal plasma leptin levels and their relationship to insulin and glugose in gestation onset diabetes(J).Cynecol Obstet lnvest, 2001, 51(1):17-21.
62 Kim K H, Lee K,Moon YS, et al.Cystine-rich adipose tissue-specific secretory factor inhibits adipocyte differenciation (J). J Biol chem, 2001,276 (14):11252-11256.
63 Chosh S,Singh AK, Antna B,et al. The genomic organization of mouse resistin reveals major differences from the human resistin:functional implications[J]. Gene, 2003, 305(1):27-34.
64 Moore GB, Chapman H,Holder JC,et al. Differential regulation of adipocytokine mRNAs by rosiglitazone in db/db mice [J].Biocbem Biophys Res Commun, 2001,286(4):735-741
65 Way JM,Gorgun CZ, Tong Q, et al. Adipose tissue resistin expression is severely suppressed in obesity and stimulated by PPARr agonist [J] . J Biol Chem, 2001, 276(28):25651-25653
66 Steppan CM, Bailey ST, Bhat S, et al.The hormone resistin links obesity to diabetes[J].Nature,2001,409(6818):307-312.
67 Steppan CM,Brown EJ,Wright CM,el al,A family of tissue specific resistin like molecules[J].Proc Natl Acad Sci USA,2001,98(2):502-506
68 McTeman CL,McTeman PG,Herte AL,et al.Resistin,central obeisty and 2 diabetes [J].Lancet,2002,359(9300):46-48
69 王学晶,徐国宾,朱立华,健康人、单纯性肥胖、糖尿病和甲亢患者的血浆reisiti 水平研究[J].中华检验医学杂志,2001,24(6):359-362
70 张建梁,秦水文,郑兴,等.人血清抵抗素水平与体脂含量和血糖及血压的相关性研究[J].中华医学杂志,2002,8(23):1609-1612.
71 Rajah M W,Qi Y,Pa et al.Regulation of -Men aperssica and circulating levels in obesity,diabetes,and fastingtJ]—Diabetes,2004,53(7):1671-1679
72 周咏明,余美霞,薛克营,等.皮下脂肪和胎盘的抵抗素表达及与胰岛素抵抗的关系.中国实用内科杂志.2005,25(11):972-974