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胎盘葡萄糖的转运及调控机制
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Abstract:
妊娠期胰岛素抵抗(IR)是一种适应性生理现象，但过度IR可导致妊娠期糖尿病(GDM)，增加母婴并发症风险。研究表明，炎症因子(如TNF-α、HMGB1)、脂肪因子(如瘦素、脂联素)及维生素D等通过调控胰岛素信号通路(如PI3K/Akt和Ras-MAPK途径)，影响GLUT的表达与功能，进而参与GDM的发生与发展。本文系统综述了妊娠期糖代谢的调控机制及其影响因素，为GDM的预防与治疗提供理论依据，并指出未来研究方向。
Insulin resistance (IR) in pregnancy is an adaptive physiologic phenomenon, but excessive IR can lead to gestational diabetes mellitus (GDM) and increase the risk of maternal and infant complications. Studies have shown that inflammatory factors (e.g., TNF-α, HMGB1), adipokines (e.g., leptin, lipocalin), and vitamin D affect the expression and function of GLUT through the modulation of insulin signaling pathways (e.g., the PI3K/Akt and Ras-MAPK pathways), which are then involved in the occurrence and development of GDM. This paper systematically reviews the regulatory mechanisms of glucose metabolism and its influencing factors during pregnancy, provides a theoretical basis for the prevention and treatment of GDM, and points out the direction of future research.
| [1] | 陈叙村. 孕期血糖、尿糖水平86例分析[J]. 上海预防医学, 2009, 21(6): 270. |
| [2] | Buchanan, T.A., Xiang, A., Kjos, S.L., Lee, W.P., Trigo, E., Nader, I., et al. (1998) Gestational Diabetes: Antepartum Characteristics That Predict Postpartum Glucose Intolerance and Type 2 Diabetes in Latino Women. Diabetes, 47, 1302-1310. https://doi.org/10.2337/diab.47.8.1302 |
| [3] | 姜洁璇, 孙磊, 金镇, 等. 性激素结合球蛋白和葡萄糖转运蛋白在妊娠期糖尿病胎盘组织中的表达及相关性[J]. 中国医科大学学报, 2015, 44(1): 5-9. |
| [4] | 马晓鹏, 杨慧霞. 妊娠合并糖代谢异常孕妇胎盘内葡萄糖转运蛋白表达的变化[J]. 中华围产医学杂志, 2008, 11(6): 373-376. |
| [5] | Zhang, B., Jin, Z., Sun, L., Zheng, Y., Jiang, J., Feng, C., et al. (2016) Expression and Correlation of Sex Hormone-Binding Globulin and Insulin Signal Transduction and Glucose Transporter Proteins in Gestational Diabetes Mellitus Placental Tissue. Diabetes Research and Clinical Practice, 119, 106-117. https://doi.org/10.1016/j.diabres.2016.07.003 |
| [6] | Stanirowski, P.J., Szukiewicz, D., Pyzlak, M., Abdalla, N., Sawicki, W. and Cendrowski, K. (2016) 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. Endocrine, 55, 799-808. https://doi.org/10.1007/s12020-016-1202-4 |
| [7] | Kokk, K., Verajankorva, E., Laato, M., Wu, X., Tapfer, H. and Pollanen, P. (2005) Expression of Insulin Receptor Substrates 1-3, Glucose Transporters GLUT-1-4, Signal Regulatory Protein 1α, Phosphatidylinositol 3-Kinase and Protein Kinase B at the Protein Level in the Human Testis. Anatomical Science International, 80, 91-96. https://doi.org/10.1111/j.1447-073x.2005.00091.x |
| [8] | Perrin, A.J., Gunda, M., Yu, B., Yen, K., Ito, S., Forster, S., et al. (2012) Noncanonical Control of C. elegans Germline Apoptosis by the Insulin/IGF-1 and Ras/MAPK Signaling Pathways. Cell Death & Differentiation, 20, 97-107. https://doi.org/10.1038/cdd.2012.101 |
| [9] | Leiria, L.O., Sollon, C., Báu, F.R., Mónica, F.Z., D’Ancona, C.L., De Nucci, G., et al. (2013) Expression of Concern: Insulin Relaxes Bladder via PI3K/AKT/eNOS Pathway Activation in Mucosa: Unfolded Protein Response‐Dependent Insulin Resistance as a Cause of Obesity‐Associated Overactive Bladder. The Journal of Physiology, 591, 2259-2273. https://doi.org/10.1113/jphysiol.2013.251843 |
| [10] | Mi, Y., Zhang, W., Tian, H., Li, R., Huang, S., Li, X., et al. (2018) EGCG Evokes Nrf2 Nuclear Translocation and Dampens PTP1B Expression to Ameliorate Metabolic Misalignment under Insulin Resistance Condition. Food & Function, 9, 1510-1523. https://doi.org/10.1039/c7fo01554b |
| [11] | Kubota, T., Kubota, N. and Kadowaki, T. (2017) Imbalanced Insulin Actions in Obesity and Type 2 Diabetes: Key Mouse Models of Insulin Signaling Pathway. Cell Metabolism, 25, 797-810. https://doi.org/10.1016/j.cmet.2017.03.004 |
| [12] | Huang, X., Liu, G., Guo, J. and Su, Z. (2018) The PI3K/AKT Pathway in Obesity and Type 2 Diabetes. International Journal of Biological Sciences, 14, 1483-1496. https://doi.org/10.7150/ijbs.27173 |
| [13] | 杨敏, 张静, 赵喜花. 妊娠糖尿病患者脂肪组织中IRS-1、IRS-2、Omentin-1表达与胰岛素抵抗[J]. 中国计划生育学杂志, 2019, 27(9): 1159-1162. |
| [14] | 冯卫红, 王艳霞, 计静, 等. IRS-1和GLUT4在妊娠期糖尿病患者胎盘组织中的表达水平及其临床意义[J]. 中国妇产科临床杂志, 2020, 21(3): 251-253. |
| [15] | 赵静. GDM患者胎盘脂肪因子及炎症因子水平及与母体糖脂代谢相关性研究[J]. 中国性科学, 2020, 29(3): 50-54. |
| [16] | Kinalski, M., Telejko, B., Kuźmicki, M., Krętowski, A. and Kinalska, I. (2005) Tumor Necrosis Factor Alpha System and Plasma Adiponectin Concentration in Women with Gestational Diabetes. Hormone and Metabolic Research, 37, 450-454. https://doi.org/10.1055/s-2005-870238 |
| [17] | Kirwan, J.P., Hauguel-De Mouzon, S., Lepercq, J., Challier, J., Huston-Presley, L., Friedman, J.E., et al. (2002) TNF-α Is a Predictor of Insulin Resistance in Human Pregnancy. Diabetes, 51, 2207-2213. https://doi.org/10.2337/diabetes.51.7.2207 |
| [18] | 李素平. TNF-α对早孕滋养细胞激素分泌及胰岛素信号蛋白的影响[D]: [硕士学位论文]. 哈尔滨: 黑龙江中医药大学, 2007. |
| [19] | 杨斌, 葛迎春, 吉冬梅, 等. 胎盘及脂肪组织中HMGB1表达与胰岛素抵抗程度及产后糖代谢异常的相关性研究[J]. 中国计划生育和妇产科, 2022, 14(3): 84-88. |
| [20] | Jiang, Y. and Steinle, J.J. (2018) HMGB1 Inhibits Insulin Signalling through TLR4 and RAGE in Human Retinal Endothelial Cells. Growth Factors, 36, 164-171. https://doi.org/10.1080/08977194.2018.1539393 |
| [21] | Liu, L., Jiang, Y. and Steinle, J.J. (2017) Inhibition of HMGB1 Protects the Retina from Ischemia-Reperfusion, as Well as Reduces Insulin Resistance Proteins. PLOS ONE, 12, e0178236. https://doi.org/10.1371/journal.pone.0178236 |
| [22] | Peng, H., Li, H., Lin, S., Zeng, W., Lin, C., Lin, K., et al. (2018) Caveolin-1 Was Required for Glargine to Improve Insulin Sensitivity and Activate PI3K/AKT Pathway in Visceral Adipose Tissue of Type 2 Diabetic Mice. Diabetes, 67, 2423-PUB. https://doi.org/10.2337/db18-2423-pub |
| [23] | Jayabalan, N., Lai, A., Ormazabal, V., Adam, S., Guanzon, D., Palma, C., et al. (2018) Adipose Tissue Exosomal Proteomic Profile Reveals a Role on Placenta Glucose Metabolism in Gestational Diabetes Mellitus. The Journal of Clinical Endocrinology & Metabolism, 104, 1735-1752. https://doi.org/10.1210/jc.2018-01599 |
| [24] | 油红捷, 闫韶飞, 丁卫. 脂肪因子visfatin的调节与功能多样性[J]. 生物化学与生物物理进展, 2008, 35(12): 1351-1357. |
| [25] | 姜文英. 妊娠期糖尿病患者分娩前后visfatin变化以及与胰岛素抵抗相关研究[D]: [硕士学位论文]. 杭州: 浙江大学, 2012. |
| [26] | Rowan, J.A., Rush, E.C., Plank, L.D., Lu, J., Obolonkin, V., Coat, S., et al. (2018) Metformin in Gestational Diabetes: The Offspring Follow-Up (MiG TOFU): Body Composition and Metabolic Outcomes at 7-9 Years of Age. BMJ Open Diabetes Research & Care, 6, e000456. https://doi.org/10.1136/bmjdrc-2017-000456 |
| [27] | 王伟, 张静, 浦春. 妊娠糖尿病患者血清、脐血及胎盘组织中Visfatin和Chemerin的表达与胰岛素抵抗发生机制的研究[J]. 现代检验医学杂志, 2022, 37(1): 21-27. |
| [28] | 王颖, 佟俊旺, 盛佳曦, 等. 血清瘦素、25羟维生素D水平与2型糖尿病下肢血管病变关系的研究[J]. 中国糖尿病杂志, 2016, 24(4): 328-330. |
| [29] | 张斌, 郭刚, 汪蓓蕾, 等. 老年2型糖尿病患者糖化血红蛋白水平与血糖及胰岛素敏感性的关系[J]. 中国老年学杂志, 2017, 37(6): 1378-1380. |
| [30] | 陈利春, 陈冠军, 叶俊良, 等. 妊娠期糖尿病患者脂肪细胞因子与炎症的相关性分析[J]. 安徽医科大学学报, 2012, 47(7): 842-845. |
| [31] | 李素芬. 瘦素对早孕滋养细胞胰岛素受体、胰岛素受体底物-1作用的实验研究[D]: [硕士学位论文]. 重庆: 第三军医大学, 2011. |
| [32] | Miehle, K., Stepan, H. and Fasshauer, M. (2011) Leptin, Adiponectin and Other Adipokines in Gestational Diabetes Mellitus and Pre‐Eclampsia. Clinical Endocrinology, 76, 2-11. https://doi.org/10.1111/j.1365-2265.2011.04234.x |
| [33] | Phillips, A. and Cobbold, C. (2014) A Comparison of the Effects of Aerobic and Intense Exercise on the Type 2 Diabetes Mellitus Risk Marker Adipokines, Adiponectin and Retinol Binding Protein-4. International Journal of Chronic Diseases, 2014, Article ID: 358058. https://doi.org/10.1155/2014/358058 |
| [34] | Christou, G., Tselepis, A. and Kiortsis, D. (2011) The Metabolic Role of Retinol Binding Protein 4: An Update. Hormone and Metabolic Research, 44, 6-14. https://doi.org/10.1055/s-0031-1295491 |
| [35] | Duggirala, R., Blangero, J., Almasy, L., Dyer, T.D., Williams, K.L., Leach, R.J., et al. (1999) Linkage of Type 2 Diabetes Mellitus and of Age at Onset to a Genetic Location on Chromosome 10q in Mexican Americans. The American Journal of Human Genetics, 64, 1127-1140. https://doi.org/10.1086/302316 |
| [36] | Graham, T.E., Yang, Q., Blüher, M., Hammarstedt, A., Ciaraldi, T.P., Henry, R.R., et al. (2006) Retinol-Binding Protein 4 and Insulin Resistance in Lean, Obese, and Diabetic Subjects. New England Journal of Medicine, 354, 2552-2563. https://doi.org/10.1056/nejmoa054862 |
| [37] | Aeberli, I., Biebinger, R., Lehmann, R., l’Allemand, D., Spinas, G.A. and Zimmermann, M.B. (2007) Serum Retinol-Binding Protein 4 Concentration and Its Ratio to Serum Retinol Are Associated with Obesity and Metabolic Syndrome Components in Children. The Journal of Clinical Endocrinology & Metabolism, 92, 4359-4365. https://doi.org/10.1210/jc.2007-0468 |
| [38] | Yang, Q., Graham, T.E., Mody, N., Preitner, F., Peroni, O.D., Zabolotny, J.M., et al. (2005) Serum Retinol Binding Protein 4 Contributes to Insulin Resistance in Obesity and Type 2 Diabetes. Nature, 436, 356-362. https://doi.org/10.1038/nature03711 |
| [39] | 巫小燕, 李锐, 吴丽群, 等. 妊娠期糖尿病患者血清NUCB／nesfatin-1水平的变化[J]. 实用医学杂志, 2014, 30(6): 912-914. |
| [40] | Li, X., Yan, C., Fan, Y., Yang, J. and Zhao, S. (2020) NUCB2 Polymorphisms Are Associated with an Increased Risk for Type 2 Diabetes in the Chinese Population. Annals of Translational Medicine, 8, 290-290. https://doi.org/10.21037/atm.2020.03.02 |
| [41] | Li, Z., Gao, L., Tang, H., Yin, Y., Xiang, X., Li, Y., et al. (2013) Peripheral Effects of Nesfatin-1 on Glucose Homeostasis. PLOS ONE, 8, e71513. https://doi.org/10.1371/journal.pone.0071513 |
| [42] | Vu, V., Bui, P., Eguchi, M., Xu, A. and Sweeney, G. (2013) Globular Adiponectin Induces LKB1/AMPK-Dependent Glucose Uptake via Actin Cytoskeleton Remodeling. Journal of Molecular Endocrinology, 51, 155-165. https://doi.org/10.1530/jme-13-0059 |
| [43] | 陈冬, 杨宁宁, 陈明卫, 等. 骨骼肌源性脂联素通过p38MAPK信号通路影响骨骼肌胰岛素抵抗模型中GLUT4表达的研究[C]//安徽省医学会内分泌糖尿病学第十四次学术年会论文集. 合肥: 安徽医科大学第一附属医院, 2012: 445-446. |
| [44] | Greulich, S., Chen, W.J.Y., Maxhera, B., Rijzewijk, L.J., van der Meer, R.W., Jonker, J.T., et al. (2013) Cardioprotective Properties of Omentin-1 in Type 2 Diabetes: Evidence from Clinical and in Vitro Studies. PLOS ONE, 8, e59697. https://doi.org/10.1371/journal.pone.0059697 |
| [45] | 潘宝龙, 马润玫. 转染人源Omentin-1、Vaspin 妊娠期糖尿病脂肪细胞胰岛素受体底物和磷脂酰肌醇3激酶表达变化[J]. 山东医药, 2016, 56(35): 9-12. |
| [46] | Mohamad, M.I., El-Sherbeny, E.E. and Bekhet, M.M. (2015) The Effect of Vitamin D Supplementation on Glycemic Control and Lipid Profile in Patients with Type 2 Diabetes Mellitus. Journal of the American College of Nutrition, 35, 399-404. https://doi.org/10.1080/07315724.2015.1026427 |
| [47] | 王哲. 维生素D对妊娠糖尿病小鼠胎盘组织中蛋白酪氨酸磷酸酶-1B、磷脂酰肌醇3激酶及葡萄糖转运体-4表达的影响[D]: [硕士学位论文]. 遵义: 遵义医科大学, 2020. |
| [48] | 杨晓煜, 黄燕芳. 传代培养对供核细胞胰岛素样生长因子Ⅱ基因表达的影响[J]. 中国现代医生, 2008, 46(36): 1-3, 10. |
| [49] | Guo, L., Choufani, S., Ferreira, J., Smith, A., Chitayat, D., Shuman, C., et al. (2008) Altered Gene Expression and Methylation of the Human Chromosome 11 Imprinted Region in Small for Gestational Age (SGA) Placentae. Developmental Biology, 320, 79-91. https://doi.org/10.1016/j.ydbio.2008.04.025 |
| [50] | Morali, O.G., Jouneau, A., McLaughlin, K.J., Thiery, J.P. and Larue, L. (2000) IGF-II Promotes Mesoderm Formation. Developmental Biology, 227, 133-145. https://doi.org/10.1006/dbio.2000.9875 |
| [51] | Liu, Y., Dong, N., Miao, J., Li, C., Wang, X. and Ruan, J. (2019) Lin28 Promotes Dental Pulp Cell Proliferation via Upregulation of Cyclin-Dependent Proteins and Interaction with Let-7a/IGF2BP2 Pathways. Biomedicine & Pharmacotherapy, 113, Article 108742. https://doi.org/10.1016/j.biopha.2019.108742 |
| [52] | Lopez-Tello, J., Yong, H.E.J., Sandovici, I., Dowsett, G.K.C., Christoforou, E.R., Salazar-Petres, E., et al. (2023) Fetal Manipulation of Maternal Metabolism Is a Critical Function of the Imprinted Igf2 Gene. Cell Metabolism, 35, 1195-1208.E6. https://doi.org/10.1016/j.cmet.2023.06.007 |
| [53] | Xiao, L. and Zhao, F. (2023) Microbial Transmission, Colonisation and Succession: From Pregnancy to Infancy. Gut, 72, 772-786. https://doi.org/10.1136/gutjnl-2022-328970 |
| [54] | Crusell, M.K.W., Hansen, T.H., Nielsen, T., Allin, K.H., Rühlemann, M.C., Damm, P., et al. (2018) Gestational Diabetes Is Associated with Change in the Gut Microbiota Composition in Third Trimester of Pregnancy and Postpartum. Microbiome, 6, Article No. 89. https://doi.org/10.1186/s40168-018-0472-x |
| [55] | Bacos, K., Gillberg, L., Volkov, P., Olsson, A.H., Hansen, T., Pedersen, O., et al. (2016) Blood-Based Biomarkers of Age-Associated Epigenetic Changes in Human Islets Associate with Insulin Secretion and Diabetes. Nature Communications, 7, Article No. 11089. https://doi.org/10.1038/ncomms11089 |
