|
|
脂肪因子Apelin与妊娠期糖尿病发病机制的研究进展
|
Abstract:
妊娠期糖尿病(GDM)是最常见的围产期并发症之一，其发病机制尚未明确，可能是由肥胖、胰岛素抵抗(IR)及炎症反应等多因素共同作用的结果。Apelin作为新型脂肪因子，与肥胖、胰岛素抵抗及炎症反应关系密切，可能参与GDM的病理生理机制中。研究表明，Apelin具有降糖、改善胰岛素敏感性等作用，有望成为GDM治疗的新靶点。
Gestational diabetes mellitus (GDM) is one of the most common perinatal complications. However, its pathogenesis is not clear, which may be the result of multiple factors such as obesity, insulin resistance (IR) and inflammatory response. As a novel adipokine, Apelin is closely related to obesity, insulin resistance and inflammation, and may be involved in the pathophysiology of GDM. Studies have shown that Apelin has the effects of reducing blood sugar and improving insulin sensitivity, and is expected to become a new target for GDM treatment.
| [1] | Gao, C., Sun, X., Lu, L., Liu, F. and Yuan, J. (2018) Prevalence of Gestational Diabetes Mellitus in Mainland China: A Systematic Review and Meta‐Analysis. Journal of Diabetes Investigation, 10, 154-162. https://doi.org/10.1111/jdi.12854 |
| [2] | Ye, W., Luo, C., Huang, J., Li, C., Liu, Z. and Liu, F. (2022) Gestational Diabetes Mellitus and Adverse Pregnancy Outcomes: Systematic Review and Meta-Analysis. BMJ, 377, e067946. https://doi.org/10.1136/bmj-2021-067946 |
| [3] | Wang, Y., Wu, H., Ding, H., Li, Y., Wang, Z., Li, F., et al. (2012) Changes of Insulin Resistance and β‐Cell Function in Women with Gestational Diabetes Mellitus and Normal Pregnant Women during Mid‐ and Late Pregnant Period: A Case-Control Study. Journal of Obstetrics and Gynaecology Research, 39, 647-652. https://doi.org/10.1111/j.1447-0756.2012.02009.x |
| [4] | Fasshauer, M. and Blüher, M. (2015) Adipokines in Health and Disease. Trends in Pharmacological Sciences, 36, 461-470. https://doi.org/10.1016/j.tips.2015.04.014 |
| [5] | Tatemoto, K., Hosoya, M., Habata, Y., Fujii, R., Kakegawa, T., Zou, M., et al. (1998) Isolation and Characterization of a Novel Endogenous Peptide Ligand for the Human APJ Receptor. Biochemical and Biophysical Research Communications, 251, 471-476. https://doi.org/10.1006/bbrc.1998.9489 |
| [6] | Lee, D.K., Cheng, R., Nguyen, T., Fan, T., Kariyawasam, A.P., Liu, Y., et al. (2000) Characterization of Apelin, the Ligand for the APJ Receptor. Journal of Neurochemistry, 74, 34-41. https://doi.org/10.1046/j.1471-4159.2000.0740034.x |
| [7] | Carpéné, C., Dray, C., Attané, C., Valet, P., Portillo, M.P., Churruca, I., et al. (2007) Expanding Role for the Apelin/APJ System in Physiopathology. Journal of Physiology and Biochemistry, 63, 358-373. https://doi.org/10.1007/bf03165767 |
| [8] | Malchow, J., Eberlein, J., Li, W., Hogan, B.M., Okuda, K.S. and Helker, C.S.M. (2024) Neural Progenitor-Derived Apelin Controls Tip Cell Behavior and Vascular Patterning. Science Advances, 10, eadk1174. https://doi.org/10.1126/sciadv.adk1174 |
| [9] | Fasshauer, M., Blüher, M. and Stumvoll, M. (2014) Adipokines in Gestational Diabetes. The Lancet Diabetes & Endocrinology, 2, 488-499. https://doi.org/10.1016/s2213-8587(13)70176-1 |
| [10] | Higuchi, K., Masaki, T., Gotoh, K., Chiba, S., Katsuragi, I., Tanaka, K., et al. (2007) Apelin, an APJ Receptor Ligand, Regulates Body Adiposity and Favors the Messenger Ribonucleic Acid Expression of Uncoupling Proteins in Mice. Endocrinology, 148, 2690-2697. https://doi.org/10.1210/en.2006-1270 |
| [11] | Yue, P., Jin, H., Xu, S., Aillaud, M., Deng, A.C., Azuma, J., et al. (2011) Apelin Decreases Lipolysis via Gq, Gi, and AMPK-Dependent Mechanisms. Endocrinology, 152, 59-68. https://doi.org/10.1210/en.2010-0576 |
| [12] | El Wakeel, M.A., El-Kassas, G.M., Kamhawy, A.H., Galal, E.M., Nassar, M.S., Hammad, E.M., et al. (2018) Serum Apelin and Obesity-Related Complications in Egyptian Children. Open Access Macedonian Journal of Medical Sciences, 6, 1354-1358. https://doi.org/10.3889/oamjms.2018.312 |
| [13] | Yalçın, T., Oğuz, S.H., Bayraktar, M. and Rakıcıoğlu, N. (2021) Anthropometric Measurements and Serum TNF-α, IL-6 and Adiponectin in Type 2 Diabetes. Diabetology International, 13, 396-406. https://doi.org/10.1007/s13340-021-00553-y |
| [14] | Zhao, X., Niu, Y., Zhao, X., Ruan, H., Xiang, Y., Wang, L., et al. (2023) Associations between Serum TNF-α, IL-6, hs-CRP and GLMD in Obese Children and Adolescents: A Cross-Sectional Study. Diabetes, Metabolic Syndrome and Obesity, 16, 3915-3923. https://doi.org/10.2147/dmso.s434482 |
| [15] | Yu, S., Zhang, Y., Li, M.Z., et al. (2012) Chemerin and Apelin Are Positively Correlated with Inflammation in Obese Type 2 Diabetic Patients. Chinese Medical Journal, 125, 3440-3444. |
| [16] | Peng, Q., Zhou, J., Xu, Z., Zhao, Q., Li, Z. and Zhao, Q. (2022) Apelin-13 Ameliorates LPS-Induced BV-2 Microglia Inflammatory Response through Promoting Autophagy and Inhibiting H3K9ac Enrichment of TNF-α and IL-6 Promoter. Acta Neurobiologiae Experimentalis, 82, 65-76. https://doi.org/10.55782/ane-2022-006 |
| [17] | Wei, Y.F., Yin, P., Liu, L., et al. (2019) Effects of APELIN-13 on the Expression of IL-6, TNF-α, and IFN-γ in Rats with Experimental Autoimmune Neuritis. Journal of Biological Regulators and Homeostatic Agents, 33, 1369-1376. |
| [18] | Castan-Laurell, I., El Boustany, R., Pereira, O., Potier, L., Marre, M., Fumeron, F., et al. (2019) Plasma Apelin and Risk of Type 2 Diabetes in a Cohort from the Community. Diabetes Care, 43, e15-e16. https://doi.org/10.2337/dc19-1865 |
| [19] | Noori-Zadeh, A., Bakhtiyari, S., Khanjari, S., Haghani, K. and Darabi, S. (2019) Elevated Blood Apelin Levels in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Diabetes Research and Clinical Practice, 148, 43-53. https://doi.org/10.1016/j.diabres.2018.12.012 |
| [20] | Mund, C., Kellellu, C.K., Rattan, R., Mahapatra, S., Lamare, A.A. and Jena, S. (2023) Study of Serum Apelin and Insulin Resistance in Type 2 Diabetes Mellitus Patients with or without Obesity. Cureus, 15, e43401. https://doi.org/10.7759/cureus.43401 |
| [21] | McIntyre, H.D., Catalano, P., Zhang, C., Desoye, G., Mathiesen, E.R. and Damm, P. (2019) Gestational Diabetes Mellitus. Nature Reviews Disease Primers, 5, Article No. 47. https://doi.org/10.1038/s41572-019-0098-8 |
| [22] | Alwash, S.M., McIntyre, H.D. and Mamun, A. (2021) The Association of General Obesity, Central Obesity and Visceral Body Fat with the Risk of Gestational Diabetes Mellitus: Evidence from a Systematic Review and Meta-Analysis. Obesity Research & Clinical Practice, 15, 425-430. https://doi.org/10.1016/j.orcp.2021.07.005 |
| [23] | Pérez-López, F.R., Wu, J., Yao, L., López-Baena, M.T., Pérez-Roncero, G.R. and Varikasuvu, S.R. (2022) Apelin Levels in Pregnant Women with and without Gestational Diabetes Mellitus: A Collaborative Systematic Review and Meta-Analysis. Gynecological Endocrinology, 38, 803-812. https://doi.org/10.1080/09513590.2022.2114450 |
| [24] | de Mendonça, E.L.S.S., Fragoso, M.B.T., de Oliveira, J.M., Xavier, J.A., Goulart, M.O.F. and de Oliveira, A.C.M. (2022) Gestational Diabetes Mellitus: The Crosslink among Inflammation, Nitroxidative Stress, Intestinal Microbiota and Alternative Therapies. Antioxidants, 11, Article 129. https://doi.org/10.3390/antiox11010129 |
| [25] | Li, Y., Long, D., Liu, J., Qiu, D., Wang, J., Cheng, X., et al. (2020) Gestational Diabetes Mellitus in Women Increased the Risk of Neonatal Infection via Inflammation and Autophagy in the Placenta. Medicine, 99, e22152. https://doi.org/10.1097/md.0000000000022152 |
| [26] | Arani Hessari, F., Sharifi, M., Yousefifard, M., Gholamzadeh, R., Nazarinia, D. and Aboutaleb, N. (2022) Apelin-13 Attenuates Cerebral Ischemia/Reperfusion Injury through Regulating Inflammation and Targeting the JAK2/STAT3 Signaling Pathway. Journal of Chemical Neuroanatomy, 126, Article 102171. https://doi.org/10.1016/j.jchemneu.2022.102171 |
| [27] | He, X., Liu, C., Peng, J., Li, Z., Li, F., Wang, J., et al. (2021) COVID-19 Induces New-Onset Insulin Resistance and Lipid Metabolic Dysregulation via Regulation of Secreted Metabolic Factors. Signal Transduction and Targeted Therapy, 6, Article No. 427. https://doi.org/10.1038/s41392-021-00822-x |
| [28] | Attané, C., Foussal, C., Le Gonidec, S., Benani, A., Daviaud, D., Wanecq, E., et al. (2012) Apelin Treatment Increases Complete Fatty Acid Oxidation, Mitochondrial Oxidative Capacity, and Biogenesis in Muscle of Insulin-Resistant Mice. Diabetes, 61, 310-320. https://doi.org/10.2337/db11-0100 |
| [29] | Bertrand, C., Pradère, J., Geoffre, N., Deleruyelle, S., Masri, B., Personnaz, J., et al. (2018) Chronic Apelin Treatment Improves Hepatic Lipid Metabolism in Obese and Insulin-Resistant Mice by an Indirect Mechanism. Endocrine, 60, 112-121. https://doi.org/10.1007/s12020-018-1536-1 |
| [30] | Dray, C., Knauf, C., Daviaud, D., Waget, A., Boucher, J., Buléon, M., et al. (2008) Apelin Stimulates Glucose Utilization in Normal and Obese Insulin-Resistant Mice. Cell Metabolism, 8, 437-445. https://doi.org/10.1016/j.cmet.2008.10.003 |
| [31] | Guo, Y., Li, T., Liu, H., Tang, L., Li, Y., Hu, H., et al. (2020) Circulating Levels of Elabela and Apelin in the Second and Third Trimesters of Pregnancies with Gestational Diabetes Mellitus. Gynecological Endocrinology, 36, 890-894. https://doi.org/10.1080/09513590.2020.1739264 |
| [32] | 孔玉玲, 石国素, 刘慧丽, 等. 妊娠期糖尿病孕妇血清脂肪因子Apelin水平与糖脂代谢相关性[J]. 中国计划生育学杂志, 2021, 29(12): 2650-2654. |
| [33] | 杨金霞, 李玮芳, 马登琴, 等. 妊娠期糖尿病患者空腹血清FGF21、Nesfatin-1及Apelin-36水平变化与胰岛素抵抗和胰岛素细胞功能的相关性分析[J]. 中国妇产科临床杂志, 2023, 24(3): 303-304. |
| [34] | Oncul, M., Tuten, A., Erman, H., et al. (2013) Maternal and Cord Blood Apelin, Resistin and Visfatin Levels in Gestational Diabetes Mellitus. Minerva Medica, 104, 527-535. |
| [35] | Aslan, M., Celik, O., Celik, N., Turkcuoglu, I., Yilmaz, E., Karaer, A., et al. (2011) Cord Blood Nesfatin-1 and Apelin-36 Levels in Gestational Diabetes Mellitus. Endocrine, 41, 424-429. https://doi.org/10.1007/s12020-011-9577-8 |
| [36] | Dessì, A., Pravettoni, C., Cesare Marincola, F., Schirru, A. and Fanos, V. (2015) The Biomarkers of Fetal Growth in Intrauterine Growth Retardation and Large for Gestational Age Cases: From Adipocytokines to a Metabolomic All-in-One Tool. Expert Review of Proteomics, 12, 309-316. https://doi.org/10.1586/14789450.2015.1034694 |
| [37] | Cekmez, F., Canpolat, F.E., Pirgon, O., Çetinkaya, M., Aydinoz, S., Suleymanoglu, S., et al. (2011) Apelin, Vaspin, Visfatin and Adiponectin in Large for Gestational Age Infants with Insulin Resistance. Cytokine, 56, 387-391. https://doi.org/10.1016/j.cyto.2011.06.007 |
| [38] | Mayeur, S., Wattez, J., Lukaszewski, M., Lecoutre, S., Butruille, L., Drougard, A., et al. (2015) Apelin Controls Fetal and Neonatal Glucose Homeostasis and Is Altered by Maternal Undernutrition. Diabetes, 65, 554-560. https://doi.org/10.2337/db15-0228 |
| [39] | Cekmez, F., Pirgon, O., Aydemir, G., Dundar, B., Çekmez, Y., Karaoglu, A., et al. (2012) Correlation between Cord Blood Apelin and IGF-1 Levels in Retinopathy of Prematurity. Biomarkers in Medicine, 6, 821-825. https://doi.org/10.2217/bmm.12.82 |
| [40] | Hanssens, S., Marousez, L., Pécheux, O., Besengez, C., Storme, L., Deruelle, P., et al. (2022) Maternal Obesity Reduces Apelin Level in Cord Blood without Altering the Placental Apelin/Elabela-APJ System. Placenta, 128, 112-115. https://doi.org/10.1016/j.placenta.2022.09.011 |
| [41] | Aydin, S. (2010) The Presence of the Peptides Apelin, Ghrelin and Nesfatin-1 in the Human Breast Milk, and the Lowering of Their Levels in Patients with Gestational Diabetes Mellitus. Peptides, 31, 2236-2240. https://doi.org/10.1016/j.peptides.2010.08.021 |
| [42] | Gutaj, P., Sibiak, R., Jankowski, M., Awdi, K., Bryl, R., Mozdziak, P., et al. (2020) The Role of the Adipokines in the Most Common Gestational Complications. International Journal of Molecular Sciences, 21, Article 9408. https://doi.org/10.3390/ijms21249408 |
| [43] | Hu, H., He, L., Li, L. and Chen, L. (2016) Apelin/APJ System as a Therapeutic Target in Diabetes and Its Complications. Molecular Genetics and Metabolism, 119, 20-27. https://doi.org/10.1016/j.ymgme.2016.07.012 |
| [44] | Gao, L.R., Zhang, N.K., Zhang, Y., Chen, Y., Wang, L., Zhu, Y., et al. (2018) Overexpression of Apelin in Wharton’ Jelly Mesenchymal Stem Cell Reverses Insulin Resistance and Promotes Pancreatic β Cell Proliferation in Type 2 Diabetic Rats. Stem Cell Research & Therapy, 9, Article No. 339. https://doi.org/10.1186/s13287-018-1084-x |
| [45] | O’Harte, F.P.M., Parthsarathy, V., Hogg, C. and Flatt, P.R. (2018) Long-Term Treatment with Acylated Analogues of Apelin-13 Amide Ameliorates Diabetes and Improves Lipid Profile of High-Fat Fed Mice. PLOS ONE, 13, e0202350. https://doi.org/10.1371/journal.pone.0202350 |
