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On-line Access: 2023-01-10

Received: 2022-03-19

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Jun YU

https://orcid.org/0000-0003-4718-409X

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Role of melatonin receptor 1B gene polymorphism and its effect on the regulation of glucose transport in gestational diabetes mellitus


Author(s):  Lijie WEI, Yi JIANG, Peng GAO, Jingyi ZHANG, Xuan ZHOU, Shenglan ZHU, Yuting CHEN, Huiting ZHANG, Yuanyuan DU, Chenyun FANG, Jiaqi LI, Xuan GAO, Mengzhou HE, Shaoshuai WANG, Ling FENG, Jun YU

Affiliation(s):  Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; more

Corresponding email(s):  yjtj2010@163.com

Key Words:  Gestational diabetes mellitus (GDM); Melatonin receptor 1B (MTNR1B); Single nucleotide polymorphism (SNP); Glucose uptake; Glucose transporters (GLUTs); Peroxisome proliferator-activated receptor γ (PPARγ)


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Lijie WEI, Yi JIANG, Peng GAO, Jingyi ZHANG, Xuan ZHOU, Shenglan ZHU, Yuting CHEN, Huiting ZHANG, Yuanyuan DU, Chenyun FANG, Jiaqi LI, Xuan GAO, Mengzhou HE, Shaoshuai WANG, Ling FENG, Jun YU. Role of melatonin receptor 1B gene polymorphism and its effect on the regulation of glucose transport in gestational diabetes mellitus[J]. Journal of Zhejiang University Science B, 2023, 24(6): 78-88.

@article{title="Role of melatonin receptor 1B gene polymorphism and its effect on the regulation of glucose transport in gestational diabetes mellitus",
author="Lijie WEI, Yi JIANG, Peng GAO, Jingyi ZHANG, Xuan ZHOU, Shenglan ZHU, Yuting CHEN, Huiting ZHANG, Yuanyuan DU, Chenyun FANG, Jiaqi LI, Xuan GAO, Mengzhou HE, Shaoshuai WANG, Ling FENG, Jun YU",
journal="Journal of Zhejiang University Science B",
volume="24",
number="1",
pages="78-88",
year="2023",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2200136"
}

%0 Journal Article
%T Role of melatonin receptor 1B gene polymorphism and its effect on the regulation of glucose transport in gestational diabetes mellitus
%A Lijie WEI
%A Yi JIANG
%A Peng GAO
%A Jingyi ZHANG
%A Xuan ZHOU
%A Shenglan ZHU
%A Yuting CHEN
%A Huiting ZHANG
%A Yuanyuan DU
%A Chenyun FANG
%A Jiaqi LI
%A Xuan GAO
%A Mengzhou HE
%A Shaoshuai WANG
%A Ling FENG
%A Jun YU
%J Journal of Zhejiang University SCIENCE B
%V 24
%N 1
%P 78-88
%@ 1673-1581
%D 2023
%I Zhejiang University Press & Springer

TY - JOUR
T1 - Role of melatonin receptor 1B gene polymorphism and its effect on the regulation of glucose transport in gestational diabetes mellitus
A1 - Lijie WEI
A1 - Yi JIANG
A1 - Peng GAO
A1 - Jingyi ZHANG
A1 - Xuan ZHOU
A1 - Shenglan ZHU
A1 - Yuting CHEN
A1 - Huiting ZHANG
A1 - Yuanyuan DU
A1 - Chenyun FANG
A1 - Jiaqi LI
A1 - Xuan GAO
A1 - Mengzhou HE
A1 - Shaoshuai WANG
A1 - Ling FENG
A1 - Jun YU
J0 - Journal of Zhejiang University Science B
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%@ 1673-1581
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Abstract: 
Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.

褪黑素受体1B基因多态性及其对葡萄糖转运的调控在妊娠期糖尿病中的作用

韦丽杰1,江一1,高鹏1,张婧怡1,周璇1,朱盛兰1,陈玉婷1,张慧婷1,都园渊1,方晨韵1,李佳琪2,高绚3,何梦舟1,王少帅1,冯玲1,余俊1
1华中科技大学同济医学院附属同济医院妇产科,中国武汉,430030
2南昌大学附属第一医院妇产科,中国南昌,330006
3亚琛工业大学医院妇产科,德国亚琛,52074
目的:探讨褪黑素受体1B基因(MTNR1B)rs10830963位点多态性与妊娠期糖尿病(GDM)发生的关联性,以及MT2受体(由MTNR1B基因编码)在滋养细胞葡萄糖摄取和转运过程中的作用及机制。
创新点:本研究探讨了中国中部地区女性人群MTNR1B基因rs10830963位点多态性与GDM发生发展之间的关系,以及MT2受体对滋养细胞中葡萄糖摄取和转运的影响。以此在一定程度上揭示MT2受体介导的褪黑素信号与GDM孕妇的新生儿高出生体重之间的关联性及可能的作用机制。
方法:本研究采用TaqMan-MGB荧光定量聚合酶链反应(qPCR)对rs10930963位点进行基因分型,分析该位点突变与GDM发生及相关代谢指标异常的关联性。采用免疫荧光、蛋白质印迹法(western blot)和qPCR检测GDM和正常孕妇胎盘中MT2受体的表达水平。体外培养滋养细胞系HTR-8/SVneo并给予褪黑素处理,利用western blot检测褪黑素信号对滋养细胞MT2受体、葡萄糖转运体(GLUTs)和激活过氧化物酶增殖物激活受体γ(PPARγ)蛋白表达水平的影响,葡萄糖检测试剂盒检测其对滋养细胞葡萄糖消耗水平的影响。进一步利用小干扰RNA(siRNA)敲低MT2受体,并采用western blot和葡萄糖检测试剂盒分别检测滋养细胞GLUTs和PPARγ的蛋白表达水平和葡萄糖消耗水平,以此探究MT2受体在褪黑素调控葡萄糖摄取和转运中的作用。
结论:MTNR1B基因的rs10830963位点多态性与GDM发生风险增加有关。MT2受体是褪黑素促进葡萄糖摄取和转运的关键受体,该过程可能由PPARγ介导。

关键词组:妊娠期糖尿病(GDM);褪黑素受体1B(MTNR1B);单核苷酸多态性(SNP);葡萄糖摄取;葡萄糖转运体(GLUTs);激活过氧化物酶增殖物激活受体γ(PPARγ)

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