信号传导抑制因子在妊娠期糖尿病胰岛素抵抗中的作用机制研究
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摘要
目的探讨细胞因子信号传导抑制因子-3(SOCS3)及其负性调控因子TNF-α、IL-6、RBP4在妊娠期糖尿病(gestational diabetes mellitus,GDM)胰岛素抵抗中的作用机制。方法选择2017年3月—2018年10月于深圳市妇幼保健院进行手术分娩的100名孕妇,其中妊娠期糖尿病孕妇50例,正常孕妇50例。对全部孕妇进行空腹血清学检查,比较两组孕妇的FPG、HbAlc、SOCS3及其负性调控因子如TNF-α、IL-6、RBP4的差异;采用荧光实时定量PCR测定GDM组孕妇和正常组孕妇胎盘和脂肪组织中SOCS-3、TNF-α、IL-6、RBP4 mRNA的相对表达量。结果血清学试验中,GDM组孕妇各项指标均明显高于正常组孕妇,基因实验中GDM组孕妇TNF-α、IL-6、RBP4在胎盘和脂肪组织中mRNA的表达量也高于正常组孕妇。结论 SOCS-3及其负性调节因子TNF-α、IL-6、RBP4与GDM的发生、发展密切相关,在临床工作中应定期监测上述指标,对预防和治疗妊娠期糖尿病具有重要的意义。
Objective To investigate the mechanism of SOCS3 and its negative regulators TNF-α,IL-6 and RBP4 in GDM insulin resistance. Methods 100 pregnant women who underwent surgical delivery in the hospital from March,2017 to October,2018 were selected,including 50 pregnant women with gestational diabetes and 50 normal pregnant women. FPG,HbAlc,SOCS3 and their negative regulatory factors,such as TNF-α,IL-6 and RBP4,were compared between the two groups. The relative expressions of SOCS-3,TNF-α,IL-6 and RBP4 mRNA in placenta and adipose tissue of pregnant women in GDM group and normal group were determined by fluorescence real-time quantitative PCR. Results In the serological test, all the indexes of pregnant women in the GDM group were significantly higher than those in the normal group. In the gene test,the expression levels of TNF-α,IL-6 and RBP4 in placenta and adipose tissue of pregnant women in the GDM group were also higher than those in the normal group. Conclusion SOCS-3 and its negative regulators TNF-α,IL-6 and RBP4 are closely related with the occurrence and development of GDM.The indicators above should be regularly monitored in clinical work,which is of great significance for the prevention and treatment of gestational diabetes.
Objective To investigate the mechanism of SOCS3 and its negative regulators TNF-α,IL-6 and RBP4 in GDM insulin resistance. Methods 100 pregnant women who underwent surgical delivery in the hospital from March,2017 to October,2018 were selected,including 50 pregnant women with gestational diabetes and 50 normal pregnant women. FPG,HbAlc,SOCS3 and their negative regulatory factors,such as TNF-α,IL-6 and RBP4,were compared between the two groups. The relative expressions of SOCS-3,TNF-α,IL-6 and RBP4 mRNA in placenta and adipose tissue of pregnant women in GDM group and normal group were determined by fluorescence real-time quantitative PCR. Results In the serological test, all the indexes of pregnant women in the GDM group were significantly higher than those in the normal group. In the gene test,the expression levels of TNF-α,IL-6 and RBP4 in placenta and adipose tissue of pregnant women in the GDM group were also higher than those in the normal group. Conclusion SOCS-3 and its negative regulators TNF-α,IL-6 and RBP4 are closely related with the occurrence and development of GDM.The indicators above should be regularly monitored in clinical work,which is of great significance for the prevention and treatment of gestational diabetes.
引文
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[13]张洁,王方,许海燕,等.炎性因子与胰岛素抵抗[J].世界华人消化杂志,2006,14(32):142-144.
[14] P ANIL K,P SWATHI C,CHUNXIA L,et al. Growth hormone(GH)differentially regulates NF-kB activity in preadipocytes and macrophages:implications for GH’s role in adipose tissue homeostasis in obesity[J]. Journal of Physiology&Biochemistry,2014,70(2):433-440.
[15] QIN Y, GRAHAM T E, NIMESH M, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes[J]. Nature,2005,436:356.
[16] MAGHBOOLI Z,HOSSEINNEZHAD A,MIRZAEI K,et al.Association between retinol-binding protein 4 concentrations and gestational diabetes mellitus and risk of developing metabolic syndrome after pregnancy[J]. Reproductive Sciences,2010,17(2):196-201.
[17] KRZYZANOWSKA K, ZEMANY L W, SCHERNTHANER G,et al. Serum concentrations of retinol-binding protein 4 in women with and without gestational diabetes[J]. Diabetologia,2008,51(7):1115-1122.
[18] CRAIG R,CHU W S.Retinol binding protein 4 as a candidate gene for type 2 diabetes and prediabetic intermediate traits[J].Molecular Genetics&Metabolism,2007,90(3):338-344.
[19] R NN S G,HANSEN J A,KAREN L,et al. The effect of suppressor of cytokine signaling 3 on GH signaling in beta-cells.[J]. Molecular Endocrinology,2002,16(9):2124-2134.
[20] KOHJIRO U,TATSUYA K,C RONALD K. Suppressor of cytokine signaling 1(SOCS-1)and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms[J]. Molecular&Cellular Biology,2004,24(12):5434-5446.
[2]曹泽毅.中华妇产科学[M].北京,人民卫生出版社,2010.
[3] LANDON M B,MELE L,SPONQ C Y,et al. The relationship between maternal glycemia and perinatal outcome[J]. Obstetrics&Gynecology,2011,201(6):S28-S29.
[4] BELLAMY L,CASAS J P,HINGORANI A D,et al. Type 2diabetes mellitus after gestational diabetes:a systematic review and meta-analysis[J]. Lancet,2009,373:1773-1779.
[5] DEY B R,FURLANETTO R W,NISSLEY P. Suppressor of cytokine signaling(SOCS)-3 protein interacts with the insulinlike growth factor-I receptor[J]. Biochemical&Biophysical Research Communications,2000,278(1):38-43.
[6] DE AGUIAR L G,DE MATOS H J,GOMES M B.Could fasting plasma glucose be used for screening high-risk outpatients for gestational diabetes mellitus?[J]. Diabetes Care, 2001, 24(5):954.
[7] JR J P L,LAVIN B,O DONNELL N. A comparison of costs associated with screening for gestational diabetes with two-tiered and one-tiered testing protocols[J]. American Journal of Obstetrics&Gynecology,2001,184(3):363-367.
[8] J RGENSEN L G M,TINE S,IVAN B,et al. Fasting and postglucose load--reference limits for peripheral venous plasma glucose concentration in pregnant women[J]. Clinical Chemistry&Laboratory Medicine,2003,41(2):187-199.
[9] CAIO PEREZ G, MARIA REGINA T, SANDRA MARIA A,et al. Cytokine levels in gestational diabetes mellitus:a systematic review of the literature[J]. American Journal of Reproductive Immunology,2013,69(6):545-557.
[10] XUELIAN G,HUIXIA Y,YI Z.Variations of tumor necrosis factor-α,leptin and adiponectin in mid-trimester of gestational diabetes mellitus[J].中华医学杂志(英文版),2008,121(8):701-705.
[11]刘陶,房臻,杨冬,等.炎性及脂肪细胞因子与妊娠期糖尿病发病的相关性及在产褥期的变化[J].中华妇产科杂志,2012,47(6):436-439.
[12] TELEJKO B,KUZMICKI M,ZONENBERG A,et al.Visfatin in gestational diabetes:serum level and mRNA expression in fat and placental tissue[J]. Diabetes Research and Clinical Practice,2009,84(1):68-75.
[13]张洁,王方,许海燕,等.炎性因子与胰岛素抵抗[J].世界华人消化杂志,2006,14(32):142-144.
[14] P ANIL K,P SWATHI C,CHUNXIA L,et al. Growth hormone(GH)differentially regulates NF-kB activity in preadipocytes and macrophages:implications for GH’s role in adipose tissue homeostasis in obesity[J]. Journal of Physiology&Biochemistry,2014,70(2):433-440.
[15] QIN Y, GRAHAM T E, NIMESH M, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes[J]. Nature,2005,436:356.
[16] MAGHBOOLI Z,HOSSEINNEZHAD A,MIRZAEI K,et al.Association between retinol-binding protein 4 concentrations and gestational diabetes mellitus and risk of developing metabolic syndrome after pregnancy[J]. Reproductive Sciences,2010,17(2):196-201.
[17] KRZYZANOWSKA K, ZEMANY L W, SCHERNTHANER G,et al. Serum concentrations of retinol-binding protein 4 in women with and without gestational diabetes[J]. Diabetologia,2008,51(7):1115-1122.
[18] CRAIG R,CHU W S.Retinol binding protein 4 as a candidate gene for type 2 diabetes and prediabetic intermediate traits[J].Molecular Genetics&Metabolism,2007,90(3):338-344.
[19] R NN S G,HANSEN J A,KAREN L,et al. The effect of suppressor of cytokine signaling 3 on GH signaling in beta-cells.[J]. Molecular Endocrinology,2002,16(9):2124-2134.
[20] KOHJIRO U,TATSUYA K,C RONALD K. Suppressor of cytokine signaling 1(SOCS-1)and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms[J]. Molecular&Cellular Biology,2004,24(12):5434-5446.