Downregulation of microRNA-873 attenuates insulin resistance and myocardial injury in rats with gestational diabetes mellitus by upregulating IGFBP2

2020 ◽  
Vol 318 (5) ◽  
pp. E723-E735 ◽  
Author(s):  
Na Han ◽  
Hai-Yan Fang ◽  
Jie-Xuan Jiang ◽  
Qian Xu
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Gestational Diabetes ◽  
Cardiac Function ◽  
Gestational Diabetes Mellitus ◽  
Myocardial Injury ◽  
Luciferase Assay ◽  
Oxide Content ◽  
Model Assessment ◽  
Myocardial Apoptosis

Gestational diabetes mellitus (GDM) is a metabolic disorder characterized by insulin resistance, and patients with GDM have a higher risk of cardiovascular disease. Multiple microRNAs (miRNAs) are reported to be involved in the regulation of myocardial injury. Moreover, miR-873 was predicted to target insulin-like growth factor binding protein 2 (IGFBP2) through bioinformatic analysis, which was further confirmed using a luciferase assay. Thus, our objective was to assess whether microRNA-873 (miR-873) affects insulin resistance and myocardial injury in an established GDM rat model. The GDM rats were treated with miR-875 mimic or inhibitor or IGFBP2 siRNA. The effects of miR-875 and IGFBP2 on the cardiac function, insulin resistance, and myocardial injury were evaluated by hemodynamic measurements, determination of biochemical indices of myocardium and serum, and insulin homeostatic model assessment. The results indicated that downregulation of miR-873 upregulated the expression of IGFBP2 and promoted the activation of phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) axis. With downregulation of miR-873 in GDM rats, the cardiac function was improved and the myocardial apoptosis was inhibited, coupled with elevated activity of superoxide dismutase, carbon monoxide synthase, and the nitric oxide content. In addition, the inhibition of miR-873 in GDM rats modulated the insulin resistance and reduced myocardial apoptosis. Overall, the data showed that inhibition of miR-873 by targeting IGFBP2 may regulate the insulin resistance and curtail myocardial injury in GDM rats through activating the PI3K/AKT/mTOR axis, thus providing a potential means of impeding the progression of GDM.

scholarly journals Differential Expression of MicroRNAs in Omental Adipose Tissue From Gestational Diabetes Mellitus Subjects Reveals miR-222 as a Regulator of ERα Expression in Estrogen-Induced Insulin Resistance

Endocrinology ◽  
2014 ◽  
Vol 155 (5) ◽  
pp. 1982-1990 ◽  
Author(s):  
Zhonghua Shi ◽  
Chun Zhao ◽  
Xirong Guo ◽  
Hongjuan Ding ◽  
Yugui Cui ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Differential Expression ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Luciferase Assay ◽  
Omental Adipose Tissue

Omental adipose tissue plays a central role in insulin resistance in gestational diabetes mellitus (GDM), and the molecular mechanisms leading to GDM remains vague. Evidence demonstrates that maternal hormones, such as estradiol, contribute to insulin resistance in GDM. In this study we determined the differential expression patterns of microRNAs (miRNAs) in omental adipose tissues from GDM patients and pregnant women with normal glucose tolerance using AFFX miRNA expression chips. MiR-222, 1 of 17 identified differentially expressed miRNAs, was found to be significantly up-regulated in GDM by quantitative real-time PCR (P < .01), and its expression was closely related with serum estradiol level (P < .05). Furthermore, miR-222 expression was significantly increased in 3T3-L1 adipocytes with a high concentration of 17β-estradiol stimulation (P < .01), whereas the expressions of estrogen receptor (ER)-α protein and insulin-sensitive membrane transporter glucose transporter 4 (GLUT4) protein (P < .01) were markedly reduced. In addition, ERα was shown to be a direct target of miR-222 in 3T3-L1 adipocytes by using the luciferase assay. Finally, antisense oligonucleotides of miR-222 transfection was used to silence miR-222 in 3T3-L1 adipocytes. The results showed that the expressions of ERα and GLUT4, the insulin-stimulated translocation of GLUT4 from the cytoplasm to the cell membrane and glucose uptake in mature adipocytes were dramatically increased (P < .01). In conclusion, miR-222 is a potential regulator of ERα expression in estrogen-induced insulin resistance in GDM and might be a candidate biomarker and therapeutic target for GDM.

scholarly journals Leaner Women with Impaired Insulin Secretion Accounts for about 40% of Gestational Diabetes Mellitus in Japan

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Seishi Furukawa ◽  
Yoichi Kobayashi
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Insulin Secretion ◽  
Gestational Diabetes ◽  
Glucose Tolerance ◽  
Gestational Diabetes Mellitus ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Impaired Insulin Secretion ◽  
Impaired Insulin

Aim. To identify the involvement of leanness and impaired insulin secretion with Japanese gestational diabetes mellitus (GDM). Method. A cross-sectional study was conducted comprising 219 at-risk pregnant women who underwent a 75g glucose tolerance test at a single institute in Tokyo, Japan. We identified GDM and normal glucose tolerance (NGT). The cut-off value of the homeostasis model assessment insulin resistance (HOMA-IR) for detecting GDM was determined. The GDM group was divided into subgroups according to insulin resistance based on the cut-off value of HOMA-IR. We compared the prepregnancy body mass index (BMI) and homeostasis model assessment of β-cell function (HOMA-β) between the group comprising low insulin resistance (LIR) and the group comprising high insulin resistance (HIR). Results. Seventy GDM cases and 149 NGT cases were identified. By using receiver operating characteristic curve analysis, the HOMA-IR cut-off value was determined to be 1.41. Twenty-five GDM cases (36%) were classified as LIR and forty-five GDM cases (64%) were classified as HIR. The background including indications for having 75gOGTT and the gestational age having 75gOGTT did not differ between groups. The BMI of the LIR group was significantly lower than that of the HIR group (20.9±2.8 vs. 24.4 ± 5.5, p<0.01), and the HOMA-β of the LIR group was significantly lower than that of the HIR group (95.5±30.3 vs. 146.0±70.1, p<0.01). A positive linear correlation was found between BMI and HOMA-β in cases of GDM (r=0.27, p=0.02). Conclusion. Leanness with impaired insulin secretion is deeply involved in Japanese gestational diabetes mellitus.

scholarly journals Lifestyle intervention modifies the effect of the MC4R genotype on changes in insulin resistance among women with prior gestational diabetes: Tianjin Gestational Diabetes Mellitus Prevention Program

2019 ◽  
Vol 110 (3) ◽  
pp. 750-758 ◽  
Author(s):  
Yuhang Chen ◽  
Huikun Liu ◽  
Leishen Wang ◽  
Tao Zhou ◽  
Zhaoxia Liang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Lifestyle Intervention ◽  
Prevention Program ◽  
Control Group ◽  
Model Assessment ◽  
Fasting Insulin

ABSTRACTBackgroundA history of gestational diabetes mellitus (GDM) has been related to an elevated risk of type 2 diabetes. The melanocortin-4 receptor (MC4R) genotype has been related to glycemic changes in women with prior GDM.ObjectiveThe objective of this study was to analyze whether lifestyle intervention modified the association between the MC4R genotype and changes in insulin sensitivity among women with prior GDM.MethodsWe genotyped MC4R rs6567160 and measured glucose and insulin in fasting plasma samples at baseline and during the first 2 follow-up visits in 1128 women with prior GDM. They were randomly assigned to either a 4-y lifestyle intervention involving both diet and physical activity or a control group from a randomized clinical trial, the Tianjin Gestational Diabetes Mellitus Prevention Program. We analyzed the interaction between the MC4R genotype and lifestyle intervention on changes in insulin resistance.ResultsFrom baseline to 1.28 y, the MC4R genotype was related to changes in fasting insulin, HOMA-IR, and homeostasis model assessment of β cell function (HOMA-B) in the intervention group. Each risk allele (C) of rs6567160 was associated with a 0.08-unit greater decrease in log(insulin), log(HOMA-IR), and log(HOMA-B) (P = 0.02, 0.04, and 0.04, respectively), whereas in the control group, each C allele tended to be associated with a greater increase in HOMA-IR (P = 0.09). We found significant interactions between the MC4R genotype and lifestyle intervention on 1.28-y changes in fasting insulin and HOMA-IR (P = 0.006 and 0.008, respectively), and such interaction remained significant when we analyzed the trajectory of changes in insulin and HOMA-IR from baseline to 2.55 y (both P = 0.03).ConclusionsThe exploratory results from the first 2 follow-up visits indicate that women with prior GDM carrying a diabetes-increasing MC4R genotype (CC or TC) may obtain better improvement than the TT genotype in insulin resistance through lifestyle intervention. This trial was registered at clinicaltrials.gov as NCT01554358.

scholarly journals 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

2020 ◽  
Vol 17 (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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