人类胎盘的葡萄糖转运机制及GDM对胎盘葡萄糖转运的影响

何银东; 张峻; 黄桦; 柳汝明; 王茜

doi:10.12259/j.issn.2095-610X.S20220903

人类胎盘的葡萄糖转运机制及GDM对胎盘葡萄糖转运的影响

doi: 10.12259/j.issn.2095-610X.S20220903

昆明医科大学第一附属医院临床药学科，云南昆明　650032

基金项目: 国家自然科学基金资助项目（82160297，H0416）；云南省高层次卫生计生技术人才培养专项基金资助项目（L-201614，H-2018077，H-201705，H-2018081）；云南省科技厅-昆明医科大学应用基础研究联合专项基金资助项目[2019FE001（-200），2018FE001（-167），202001AY070001-045，2018FE001（-310）]

详细信息

作者简介:
何银东（1997～），女，云南保山人，在读硕士研究生，主要从事妊娠期糖尿病患者治疗药物安全性相关的研究工作

通讯作者:
王茜，E-mail：crynner@126.com

中图分类号: R713.1
计量
- 文章访问数: 2503
- HTML全文浏览量: 2061
- PDF下载量: 30
- 被引次数: 0
出版历程
- 收稿日期: 2022-06-09
- 网络出版日期: 2022-09-07
- 刊出日期: 2022-09-29

Glucose Transport in Human Placenta and the Effect of GDM on Placental Glucose Transport

Dept. of Clinical Medicine，The 1st Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650032，China

摘要

摘要: 胎盘是将母体葡萄糖转运至子体的重要器官，正常的胎盘结构和功能为胎儿从母体有效摄取葡萄糖提供保障。胎盘上葡萄糖转运主要依赖于胎盘上的葡萄糖转运体（glucose transporters，GLUTs）。此外，胎盘自身对葡萄糖代谢也会影响经胎盘的葡萄糖转运。妊娠期糖尿病（gestational diabetes mellitus，GDM）是一种常见的妊娠期并发症。GDM患者胎盘上葡萄糖转体运功能的异常，可能是造成其子代产生不良结局的原因之一。就正常胎盘上的葡萄糖转运进行论述，并且探讨GDM患者胎盘上葡萄糖转运的改变及可能的分子机制。
- 胎盘 /
- 葡萄糖转运 /
- 葡萄糖转运体 /
- 妊娠期糖尿病
Abstract: Placenta plays an important role in the process of glucose transfer from maternal to fetus. The normal structure and function of the placenta guarantee the fetus to take up glucose effectively from maternal side over the gestation. Glucose transplacental transfer mainly depends on the glucose transporters （GLUTs）. And the placenta and other factors such as placental glucose metabolic activity could also affect the glucose transplacental transfer. Gestational diabetes mellitus （GDM） is a main complication of pregnancy. Fetal adverse outcomes from GDM patients may be caused by the abnormality of glucose transport in the placenta. This review aims to discuss the glucose transplacental transfer on the normal placenta and summarize some changes and molecular mechanism that have been reported about glucose transplacental transfer in the GDM.
- Placenta /
- Glucose transport /
- Glucose transporters /
- GDM

HTML全文

图 1 胎盘上的葡萄糖转运简图^[1]

注：K_mi ：葡萄糖的胞间转运米氏常数；K_mo ：葡萄糖的胞外转运米氏常数; [glucose] ：葡萄糖浓度。葡萄糖通过GLUTs从血糖浓度较高的母体侧扩散到血糖浓度较低的胎儿侧。母体侧血糖浓度从动脉到静脉依次是[glucose] _A > [glucose ]_B > [glucose] _C > > [glucose] _H，胎盘各个区域的葡萄糖浓度由母体侧转运进来的血糖和各个区域向胎儿侧扩散的葡萄糖共同决定。

Figure 1. Transplacental glucose transport

下载: 全尺寸图片幻灯片

参考文献(43)

[1]	Day P E,Cleal J K,Lofthouse E M,et al. What factors determine placental glucose transfer kinetics?[J]. Placenta,2013,34(10):953-958. doi: 10.1016/j.placenta.2013.07.001
[2]	Stanirowski P J,Szukiewicz D,Pyzlak M,et al. Impact of pre-gestational and gestational diabetes mellitus on the expression of glucose transporters GLUT-1,GLUT-4 and GLUT-9 in human term placenta[J]. Endocrine,2017,55(3):799-808. doi: 10.1007/s12020-016-1202-4
[3]	Illsley N P,Baumann M U. Human placental glucose transport in fetoplacental growth and metabolism[J]. Biochim Biophys Acta Mol Basis Dis,2020,1866(2):165-359.
[4]	Jansson T,Wennergren M,Illsley N P. Glucose transporter protein expression in human placenta throughout gestation and in intrauterine growth retardation[J]. J Clin Endocrinol Metab,1993,77(6):1554-1562.
[5]	Illsley N P. Placental glucose transport in diabetic pregnancy[J]. Clin Obstet Gynecol,2000,43(1):116-126. doi: 10.1097/00003081-200003000-00012
[6]	Vardhana P A,Illsley N P. Transepithelial glucose transport and metabolism in BeWo choriocarcinoma cells[J]. Placenta,2002,23(8-9):653-660. doi: 10.1053/plac.2002.0857
[7]	Brown K,Heller D S,Zamudio S,et al. Glucose transporter 3 (GLUT3) protein expression in human placenta across gestation[J]. Placenta,2011,32(12):1041-1049. doi: 10.1016/j.placenta.2011.09.014
[8]	Janzen C,Lei M Y,Cho J,et al. Placental glucose transporter 3 (GLUT3) is up-regulated in human pregnancies complicated by late-onset intrauterine growth restriction[J]. Placenta,2013,34(11):1072-1078. doi: 10.1016/j.placenta.2013.08.010
[9]	James-Allan L B,Arbet J,Teal S B,et al. Insulin stimulates GLUT4 trafficking to the syncytiotrophoblast basal plasma membrane in the human placenta[J]. J Clin Endocrinol Metab,2019,104(9):4225-4238. doi: 10.1210/jc.2018-02778
[10]	Ericsson A,Hamark B,Powell T L,et al. Glucose transporter isoform 4 is expressed in the syncytiotrophoblast of first trimester human placenta[J]. Hum Reprod,2005,20(2):521-530. doi: 10.1093/humrep/deh596
[11]	Hiden U,Glitzner E,Hartmann M,et al. Insulin and the IGF system in the human placenta of normal and diabetic pregnancies[J]. J Anat,2009,215(1):60-68. doi: 10.1111/j.1469-7580.2008.01035.x
[12]	Desoye G,Hartmann M,Blaschitz A,et al. Insulin receptors in syncytiotrophoblast and fetal endothelium of human placenta. Immunohistochemical evidence for developmental changes in distribution pattern[J]. Histochemistry,1994,101(4):277-285. doi: 10.1007/BF00315915
[13]	Augustin R,Carayannopoulos M O,Dowd L O,et al. Identification and characterization of human glucose transporter-like protein-9 (GLUT9):Alternative splicing alters trafficking[J]. J Biol Chem,2004,279(16):16229-16236. doi: 10.1074/jbc.M312226200
[14]	Gude N M,Stevenson J L,Rogers S,et al. GLUT12 expression in human placenta in first trimester and term[J]. Placenta,2003,24(5):566-570. doi: 10.1053/plac.2002.0925
[15]	Michelsen T M,Holme A M,Holm M B,et al. Uteroplacental glucose uptake and fetal glucose consumption:A quantitative study in human pregnancies[J]. J Clin Endocrinol Metab,2019,104(3):873-882. doi: 10.1210/jc.2018-01154
[16]	Hod M, Kapur A, Sacks D A, et al. The international federation of gynecology and obstetrics （FIGO） initiative on gestational diabetes mellitus: A pragmatic guide for diagnosis, management, and care [J]. Int J Gynaecol Obstet, 2015, 131（Suppl 3 ）: S173-211.
[17]	Wei Y,Yang H,Zhu W,et al. International association of diabetes and pregnancy study group criteria is suitable for gestational diabetes mellitus diagnosis:Further evidence from China[J]. Chin Med J (Engl),2014,127(20):3553-3556.
[18]	American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins-Obstetrics. Practice Bulletin No. 180:Gestational diabetes mellitus[J]. Obstet Gynecol,2017,130(1):e17-e37.
[19]	Dugas C,Perron J,Kearney M,et al. Postnatal prevention of childhood obesity in offspring prenatally exposed to gestational diabetes mellitus:Where are we now?[J]. Obes Facts,2017,10(4):396-406. doi: 10.1159/000477407
[20]	Ashfaq M,Janjua M Z,Channa M A. Effect of gestational diabetes and maternal hypertension on gross morphology of placenta[J]. J Ayub Med Coll Abbottabad,2005,17(1):44-47.
[21]	Desoye G,Cervar-Zivkovic M. Diabetes mellitus,obesity,and the placenta[J]. Obstet Gynecol Clin North Am,2020,47(1):65-79. doi: 10.1016/j.ogc.2019.11.001
[22]	Madazli R,Tuten A,Calay Z,et al. The incidence of placental abnormalities,maternal and cord plasma malondialdehyde and vascular endothelial growth factor levels in women with gestational diabetes mellitus and nondiabetic controls[J]. Gynecol Obstet Invest,2008,65(4):227-232. doi: 10.1159/000113045
[23]	Hahn T,Barth S,Weiss U,et al. Sustained hyperglycemia in vitro down-regulates the GLUT1 glucose transport system of cultured human term placental trophoblast:A mechanism to protect fetal development?[J]. Faseb J,1998,12(12):1221-1231. doi: 10.1096/fasebj.12.12.1221
[24]	Illsley N P,Sellers M C,Wright R L. Glycaemic regulation of glucose transporter expression and activity in the human placenta[J]. Placenta,1998,19(7):517-524. doi: 10.1016/S0143-4004(98)91045-1
[25]	Basak S,Vilasagaram S,Naidu K,et al. Insulin-dependent,glucose transporter 1 mediated glucose uptake and tube formation in the human placental first trimester trophoblast cells[J]. Mol Cell Biochem,2019,451(1-2):91-106. doi: 10.1007/s11010-018-3396-7
[26]	Jansson T,Ekstrand Y,Wennergren M,et al. Placental glucose transport in gestational diabetes mellitus[J]. Am J Obstet Gynecol,2001,184(2):111-116. doi: 10.1067/mob.2001.108075
[27]	Gaither K,Quraishi A N,Illsley N P. Diabetes alters the expression and activity of the human placental GLUT1 glucose transporter[J]. J Clin Endocrinol Metab,1999,84(2):695-701.
[28]	Yao G,Zhang Y,Wang D,et al. GDM-induced macrosomia is reversed by Cav-1 via AMPK-mediated fatty acid transport and GLUT1-mediated glucose transport in placenta[J]. PLoS One,2017,12(1):1-18.
[29]	Stanirowski P J,Lipa M,Bomba-Opoń D,et al. Expression of placental glucose transporter proteins in pregnancies complicated by fetal growth disorders[J]. Adv Protein Chem Struct Biol,2021(123):95-131.
[30]	Joshi N P,Mane A R,Sahay A S,et al. Role of placental glucose transporters in determining fetal growth[J]. Reprod Sci,2021,23(5):114-119.
[31]	Sciullo E,Cardellini G,Baroni M,et al. Glucose transporters (GLUT 1,GLUT 3) mRNA in human placenta of diabetic and non-diabetic pregnancies[J]. Ann Ist Super Sanita,1997,33(3):361-365.
[32]	Kainulainen H,Järvinen T,Heinonen P K. Placental glucose transporters in fetal intrauterine growth retardation and macrosomia[J]. Gynecol Obstet Invest,1997,44(2):89-92. doi: 10.1159/000291493
[33]	Valent A M,Choi H,Kolahi K S,et al. Hyperglycemia and gestational diabetes suppress placental glycolysis and mitochondrial function and alter lipid processing[J]. Faseb J,2021,35(3):e21423.
[34]	Carey E A,Albers R E,Doliboa S R,et al. AMPK knockdown in placental trophoblast cells results in altered morphology and function[J]. Stem Cells Dev,2014,23(23):2921-2930. doi: 10.1089/scd.2014.0092
[35]	Martino J,Sebert S,Segura M T,et al. Maternal body weight and gestational diabetes differentially influence placental and pregnancy outcomes[J]. J Clin Endocrinol Metab,2016,101(1):59-68. doi: 10.1210/jc.2015-2590
[36]	凌晓娟,黄震,李红霞. 孕妇体重和妊娠期糖尿病对胎盘和妊娠结局的影响[J]. 中国实验诊断学,2019,23(7):1109-1116. doi: 10.3969/j.issn.1007-4287.2019.07.001
[37]	Shang M,Wen Z. Increased placental IGF-1/mTOR activity in macrosomia born to women with gestational diabetes[J]. Diabetes Res Clin Pract,2018,146(8):211-219.
[38]	Jansson T,Aye I L,Goberdhan D C. The emerging role of mTORC1 signaling in placental nutrient-sensing[J]. Placenta,2012,33(11):e23-29.
[39]	Roos S,Lagerlöf O,Wennergren M,et al. Regulation of amino acid transporters by glucose and growth factors in cultured primary human trophoblast cells is mediated by mTOR signaling[J]. Am J Physiol Cell Physiol,2009,297(3):723-731. doi: 10.1152/ajpcell.00191.2009
[40]	Dennis P B,Jaeschke A,Saitoh M,et al. Mammalian TOR:A homeostatic ATP sensor[J]. Science,2001,294(5544):1102-1105. doi: 10.1126/science.1063518
[41]	Xu J,Lu C,Wang J,et al. Regulation of human trophoblast GLUT3 glucose transporter by mammalian target of rapamycin signaling[J]. Int J Mol Sci,2015,16(6):13815-13828.
[42]	Muralimanoharan S,Maloyan A,Myatt L. Mitochondrial function and glucose metabolism in the placenta with gestational diabetes mellitus:Role of miR-143[J]. Clin Sci (Lond),2016,130(11):931-941. doi: 10.1042/CS20160076
[43]	Baumann M U,Schneider H,Malek A,et al. Regulation of human trophoblast GLUT1 glucose transporter by insulin-like growth factor I (IGF-I)[J]. PLoS One,2014,9(8):1-28.

相关文章(20)

[1]	王秀花, 何泽然, 李志蕻, 王慧铃, 苏红艳. 脂肪乳氨基酸（17）葡萄糖（11%）注射液临床应用点评与规范、合理使用, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20230318
[2]	孙芳, 黄世英, 刘舒, 付景云. 2型糖尿病患者葡萄糖目标范围内时间与颈动脉内中膜厚度的相关性, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20230427
[3]	张帆, 郭伟昌, 谭洪, 殷和佳, 彭露萍, 赵燕, 李会芳. 葡萄糖变异参数构建糖尿病周围神经病变风险预测模型的探讨, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20230526
[4]	赵亚玲, 武坤, 王凯, 黄蓉, 何根娅, 纳玉辉, 何苗, 丁臻博, 张彩营. 妊娠期糖尿病宫内高血糖环境对子代外周炎症反应的影响, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20231110
[5]	阳情姚, 曾洁, 张卫权, 宁月, 李檬, 李湛华, 刘梅, 熊晶晶, 黄永坤. 妊娠期糖尿病与正常足月儿母亲胎盘菌群DNA的差异, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20231006
[6]	荣娜娜, 李玉凤, 任李玥, 胡月新. RP-HPLC法测定诺氟沙星葡萄糖注射液中乙二胺四乙酸二钠的含量, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20210807
[7]	代毅聪, 陈凤容, 王昆华. 谷氨酸转运体的结构、功能及其在神经精神疾病中的作用, 昆明医科大学学报.
[8]	张锦山, 沈绍聪, 李律, 王奇, 尤庶敏, 张才军. 不同葡萄糖浓度对大鼠草酸钙结石模型的影响, 昆明医科大学学报.
[9]	杨奕梅, 康玮, 范薇, 戴芙蓉, 孙宇. 孕妇不同血糖指标异常与妊娠结局的关系, 昆明医科大学学报.
[10]	苏虹, 孙洪丽, 杨君. 远程多位一体医疗管理在妊娠期糖尿病中的应用, 昆明医科大学学报.
[11]	林雁, 张京晶, 黄高贵, 张翼宇, 芮溧, 姚树祥. 昆明地区中小学学生的5-HT转运体蛋白基因(SLC6A4)与儿童品行障碍的关联性, 昆明医科大学学报.
[12]	刘惠谨, 杨莹莹, 潘景, 刘洋, 李晓毅, 周红林. 葡萄糖调节蛋白94在宫颈病变中的表达, 昆明医科大学学报.
[13]	熊晶晶, 祁文瑾, 胡红卫, 曾洁, 黄蓉, 马润玫, 刘梅, 黄永坤. 正常足月儿母亲胎盘菌群检析, 昆明医科大学学报.
[14]	张米莉. 早期综合护理干预对糖尿病孕妇的临床效果观察, 昆明医科大学学报.
[15]	雷春莲. 参芎葡萄糖注射液辅助硫酸镁治疗PIH的临床疗效分析, 昆明医科大学学报.
[16]	金镝. 高渗葡萄糖穴位注射治疗耳鸣, 昆明医科大学学报.
[17]	柴雁菁. 同型半胱氨酸对葡萄糖代谢和骨骼肌p-Akt（Ser-473)的影响, 昆明医科大学学报.
[18]	师海英. TGF-β1、β3 在子痫前期患者胎盘组织中的表达, 昆明医科大学学报.
[19]	. 正常妊娠、妊娠期糖尿病人的胰岛素抵抗状态及胰岛素分泌功能探讨, 昆明医科大学学报.
[20]	洪芸. 10%葡萄糖酸钙防治择期剖宫产术中出血84例临床观察, 昆明医科大学学报.