Relationship between tyrosine phosphorylation and protein expression of insulin receptor and insulin resistance in gestational diabetes mellitus

Aims: This study was conducted to investigate the relationship between a genetic polymorphism and the expression of melatonin receptor 1B (MTNR1B) in the placenta of Han Chinese women with gestational diabetes mellitus (GDM). Methods: In this study, 215 patients with GDM and 243 healthy controls were genotyped using direct sequencing for the MTNR1B single-nucleotide polymorphism rs10830963. The expression of MTNR1B in placenta was detected by immunohistochemistry and Western blotting. The association of rs10830963 with the expression of MTNR1B, plasma glucose, and insulin levels as well as blood lipid levels was investigated. Results: The genotype and allele frequencies of rs10830963 were significantly different between women with GDM and controls ( P < .05). Fasting blood glucose, fasting insulin, and homeostasis model assessment for insulin resistance in women with GDM with the GG and GC genotypes were significantly higher than those with the CC genotype ( P < .05). The expression level of MTNR1B in placenta was significantly higher in the GDM group than in the control group ( P < .05). The expression of MTNR1B was significantly higher in all participants with the GG and GC genotypes (1.31 [0.74]) than in pregnant women with the CC genotype (0.92 [0.52], P < .05). Conclusions: The genetic polymorphism rs10830963 in MTNR1B and its protein expression levels in placenta are associated with an increased risk of developing GDM. Furthermore, rs10830963 may tag a molecular mechanism leading to insulin resistance in Han Chinese women with GDM.

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Altered Protein Expression in Gestational Diabetes Mellitus Placentas Provides Insight into Insulin Resistance and Coagulation/Fibrinolysis Pathways

PLoS ONE ◽

10.1371/journal.pone.0044701 ◽

2012 ◽

Vol 7 (9) ◽

pp. e44701 ◽

Cited By ~ 22

Author(s):

Bin Liu ◽

Yun Xu ◽

Courtney Voss ◽

Fang-hua Qiu ◽

Ming-zhe Zhao ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Gestational Diabetes ◽

Protein Expression ◽

Gestational Diabetes Mellitus ◽

Altered Protein ◽

Insight Into

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Plasma retinol-binding protein 4 in the first and second trimester and risk of gestational diabetes mellitus in Chinese women: a nested case-control study

Nutrition & Metabolism ◽

10.1186/s12986-019-0425-9 ◽

2020 ◽

Vol 17 (1) ◽

Cited By ~ 1

Author(s):

Chuyao Jin ◽

Lizi Lin ◽

Na Han ◽

Zhiling Zhao ◽

Zheng Liu ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Binding Protein ◽

First Trimester ◽

Retinol Binding Protein ◽

Second Trimester ◽

Retinol Binding Protein 4 ◽

Plasma Retinol

Abstract Background To assess the association between plasma retinol-binding protein 4 (RBP4) levels both in the first trimester and second trimester and risk of gestational diabetes mellitus (GDM). Methods Plasma RBP4 levels and insulin were measured among 135 GDM cases and 135 controls nested within the Peking University Birth Cohort in Tongzhou. Multivariable linear regression analysis was conducted to assess the influence of RBP4 levels on insulin resistance. Conditional logistic regression models were used to compute the odds ratio (OR) and 95% confidence interval (CI) between RBP4 levels and risk of GDM. Results The GDM cases had significantly higher levels of RBP4 in the first trimester than controls (medians: 18.0 μg/L vs 14.4 μg/L; P < 0.05). Plasma RBP4 concentrations in the first and second trimester were associated with fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR), and the quantitative insulin sensitivity check index (QUICKI) in the second trimester (all P < 0.001). With adjustment for diet, physical activity, and other risk factors for GDM, the risk of GDM increased with every 1-log μg/L increment of RBP4 levels, and the OR (95% CI) was 3.12 (1.08–9.04) for RBP4 in the first trimester and 3.38 (1.03–11.08) for RBP4 in the second trimester. Conclusions Plasma RBP4 levels both in the first trimester and second trimester were dose-dependently associated with increased risk of GDM.

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The Association between Maternal/Fetal Insulin Receptor Substrate 1 Gene Polymorphism rs1801278 and Gestational Diabetes Mellitus in a Chinese Population

Gynecologic and Obstetric Investigation ◽

10.1159/000514971 ◽

2021 ◽

pp. 1-8

Author(s):

Lingling Wu ◽

Changping Fang ◽

Jun Zhang ◽

Yanchou Ye ◽

Haiyan Zhao

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gene Polymorphism ◽

Gestational Diabetes Mellitus ◽

Insulin Receptor ◽

Tolerance Test ◽

Oral Glucose ◽

Insulin Receptor Substrate ◽

Single Center ◽

Insulin Receptor Substrate 1

Objectives: Insulin receptor substrate 1 (IRS1) is a crucial factor in the insulin signaling pathway. IRS1 gene polymorphism rs1801278 in mothers has been reported to be associated with gestational diabetes mellitus (GDM). However, it is not clear whether IRS1 gene polymorphism rs1801278 in fetuses is associated with their mothers’ GDM morbidity. The purpose of this study is to analyze the association between maternal, fetal, or maternal/fetal IRS1 gene polymorphism rs1801278 and GDM risk. Design: The study was a single-center, prospective cohort study. In total, 213 pairs of GDM mothers/fetuses and 191 pairs of control mothers/fetuses were included in this study. They were recruited after they underwent oral glucose tolerance test during 24–28 weeks of gestation and followed up until delivery. All participants received the conventional interventions (diet and exercise), and no special therapy except routine treatment. Methods: A total of 213 pairs of GDM mothers/fetuses and 191 pairs of normal blood glucose pregnant mothers/fetuses were genotyped using PCR and DNA sequencing from January 2015 to September 2016. Maternal/fetal IRS1 gene polymorphism rs1801278 was analyzed and compared between 2 groups. Results: There were no significant differences in the frequency of individual mothers’ or fetuses’ IRS1 rs1801278 polymorphisms between 2 groups; if both the mothers and fetuses carried A allele, significantly lower GDM morbidity was observed in the mothers. Limitations: The sample size was relatively small as a single-center study. Conclusions: Our study suggested that maternal/fetal rs1801278 polymorphism of IRS1 is a modulating factor in GDM; both mothers/fetuses carrying the A allele of rs1801278 may protect the mothers against the development of GDM.

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