High Glucose Suppresses Cardiomyocyte Progenitor Cell Regenerative Capacity and the Role of miR-195/EZH2 Crosstalk in Gestational Diabetes Mellitus

2021 ◽  
Vol 242 ◽  
pp. 162-163
Author(s):  
Pranav Mellacheruvu ◽  
Progyaparamita Saha ◽  
Sameer Ahmad Guru ◽  
Rachana Mishra ◽  
Sudhish Sharma ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
High Glucose ◽  
Progenitor Cell ◽  
Regenerative Capacity

Abstract P456: High Glucose Suppresses Cardiomyocyte Progenitor Cell Regenerative Capacity And The Role Of Mir-195/ezh2 Crosstalk In Gestational Diabetes Mellitus

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Pranav Mellacheruvu ◽  
Progyaparamita Saha ◽  
Rachana Mishra ◽  
Sudhish Sharma ◽  
Sunjay Kaushal
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
High Glucose ◽  
Cellular Proliferation ◽  
Cell Counting ◽  
Regenerative Capacity ◽  
Expression Levels

Introduction: Gestational diabetes mellitus (GDM) is associated with a five-fold increase in congenital heart defects. It is critical to determine the biological effects of diabetes mellitus (DM) in vivo and high glucose in vitro on neonatal cardiomyocyte progenitor cells (nCPCs) to maximize their regenerative potential. In the present study we seek to investigate the roles of Mir-195 and its hypothesized target gene, enhancer of zeste homolog 2 (Ezh2), in GDM. Hypothesis: We predict that high glucose is associated with decreased cellular proliferation, viability and increased senescence through oxidative stress. We also hypothesize that expression of Mir-195 will be higher in DM-nCPCs and inhibit cell proliferation via Ezh2 silencing. Methods: We subjected nCPCs in vitro to increasing glucose concentrations; cellular proliferation, migration, reactive oxygen species generation, and apoptosis were assessed using cell counting kit-8, wound healing, dihydroethidium, and annexin assays respectively. Our in vivo experiments involved injecting four-week old female mice with streptozocin. After pairing diabetic mice with non-diabetic male mice, timed embryos at E14.5 were evaluated for viability, proliferation and characterization. mRNA expression levels of Mir-195 and Ezh2 protein levels were detected using RT-qPCR and western blot analysis respectively. Lipofectamine transfection, with siRNA inhibiting Mir-195, was performed on c-kit+ cardiac stem cells obtained from diabetic mothers. Results: We found that subjecting nCPCs in vitro to increased glucose concentration led to increased % cell death, decreased proliferation and expression of paracrine factors indicating poorer secretome quality from these cells. Our in vivo models showed that maternal diabetes impedes prenatal development as decreased expression of c-kit+/Lin- cells and ISL1+ cells and increased DHE positivity were seen in DM-nCPCs at E14.5. Expression of Mir-195 was higher in DM-nCPCs but Ezh2 mRNA and protein expression levels were significantly decreased. siRNA inhibition of Mir-195 revealed higher EZH2 expression in c-kit+ cells and concomitant increase in regenerative capacity. Conclusion: In conclusion, the viability of DM-nCPCs both in vivo and in vitro is decreased compared to NDM-nCPCs suggesting decreased postnatal regenerative capacity. Mir-195 is associated with increased apoptosis and decreased proliferation of nCPCs via abrogation of the protective effects of EZH2.

Diet and Nutritional Interventions with the Special Role of Myo-Inositol in Gestational Diabetes Mellitus Management. An Evidence-Based Critical Appraisal

2019 ◽  
Vol 25 (22) ◽  
pp. 2467-2473 ◽  
Author(s):  
Enrique Reyes-Muñoz ◽  
Federica Di Guardo ◽  
Michal Ciebiera ◽  
Ilker Kahramanoglu ◽  
Thozhukat Sathyapalan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Metabolic Diseases ◽  
Nutritional Intervention ◽  
Attractive Alternative ◽  
Special Role ◽  
Dose Frequency ◽  
Nutritional Interventions

Background: Gestational Diabetes Mellitus (GDM), defined as glucose intolerance with onset or first recognition during pregnancy, represents one of the most common maternal-fetal complications during pregnancy and it is associated with poor perinatal outcomes. To date, GDM is a rising condition over the last decades coinciding with the ongoing epidemic of obesity and Type 2 Diabetes Mellitus (T2DM). Objective: The aim of this review is to discuss the role of diet and nutritional interventions in preventing GDM with the explanation of the special role of myo-inositol (MI) in this matter. Methods: We performed an overview of the most recent literature data on the subject with particular attention to the effectiveness of diet and nutritional interventions in the prevention of GDM with the special role of MI. Results: Nutritional intervention and physical activity before and during pregnancy are mandatory in women affected by GDM. Moreover, the availability of insulin-sensitizers such as different forms of inositol has dramatically changed the scenario, allowing the treatment of several metabolic diseases, such as those related to glucose dysbalance. Although the optimal dose, frequency, and form of MI administration need to be further investigated, diet supplementation with MI appears to be an attractive alternative for the GDM prevention as well as for the reduction of GDM-related complications. Conclusion: More studies should be conducted to prove the most effective nutritional intervention in GDM. Regarding the potential effectiveness of MI, further evidence in multicenter, randomized controlled trials is needed to draw firm conclusions.

High Glucose Level Induces Cardiovascular Dysplasia During Early Embryo Development

2017 ◽  
Vol 127 (09) ◽  
pp. 590-597
Author(s):  
Yi-mei Jin ◽  
Shu-zhu Zhao ◽  
Zhao-long Zhang ◽  
Yao Chen ◽  
Xin Cheng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Reactive Oxygen Species ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
High Glucose ◽  
Reactive Oxygen ◽  
Early Embryo ◽  
Yolk Sac ◽  
Oxygen Species ◽  
Excess Reactive Oxygen Species

AbstractThe incidence of gestational diabetes mellitus (GDM) has increased dramatically amongst multiethnic population. However, how gestational diabetes mellitus damages the developing embryo is still unknown. In this study, we used yolk sac membrane (YSM) model to investigate angiogenesis in the developing chick embryo. We determined that in the presence of high glucose, it retarded the growth and extension of the embryonic vascular plexus and it also reduced the density of the vasculature in yolk sac membrane model. Using the same strategy, we used the chorioallantoic membrane (CAM) as a model to investigate the influence of high glucose on the vasculature. We established that high glucose inhibited development of the blood vessel plexus and the blood vessels formed had a narrower diameter than control vessels. Concurrent with the abnormal angiogenesis, we also examined how it impacted cardiogenesis. We determined the myocardium in the right ventricle and left atrium were significantly thicker than the control and also there was a reduction in glycogen content in cardiomyocytes. The high glucose also induced excess reactive oxygen species (ROS) production in the cardiomyocytes. We postulated that it was the excess reactive oxygen species that damaged the cardiomyocytes resulting in cardiac hyperplasia.

scholarly journals The Role of IL-37 and IL-38 in Obstetrics Abnormalities

2021 ◽  
Vol 8 ◽  
Author(s):  
Mei Wang
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Inflammatory Mediator ◽  
Inflammatory Responses ◽  
Medical Practitioners ◽  
Minimal Difference ◽  
Anti Inflammatory ◽  
Umbilical Cords

There are two fairly common complications during pregnancy, i.e., gestational diabetes mellitus (GDM) and pre-eclampsia, which are independent, but are also closely linked in prevalence in pregnant women, with potential serious adverse consequences. IL-37 and IL-38, which belong to the IL-1 superfamily, participate in anti-inflammatory responses. Dysregulation of IL-37 and IL-38 has been observed in many auto-immune diseases. IL-37 is substantially reduced in the umbilical cords and placentas of GDM subjects, but IL-37 is significantly induced in the placentas of pre-eclampsia patients, suggesting there are differential regulatory roles of IL-37 in obstetrics, despite IL-37 being an anti-inflammatory mediator. Furthermore, IL-38 is substantially increased in the umbilical cords and placentas of GDM subjects, but minimal difference is observed in the placentas from pre-eclampsia patients. These data imply that IL-38 is also regulated independently within the diseased placentas. This review provides some insight for both basic scientists and medical practitioners to manage these patients effectively.

The Role of Oxidative Stress in the Pathophysiology of Gestational Diabetes Mellitus

2011 ◽  
Vol 15 (12) ◽  
pp. 3061-3100 ◽  
Author(s):  
Martha Lappas ◽  
Ursula Hiden ◽  
Gernot Desoye ◽  
Julia Froehlich ◽  
Sylvie Hauguel-de Mouzon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus

Role of Fibroblast growth factor 21 (FGF-21) as a prognostic marker for fetal and maternal complications in patients with gestational diabetes mellitus

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Mohamed Reda Halawa ◽  
Magdy Hassan Kolaib ◽  
Salah Hussein El-Halawany ◽  
Dina Ahmed Marwan ◽  
Ola Mohamed Mostafa Shaheen
Keyword(s):  
Diabetes Mellitus ◽  
Growth Factor ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Fibroblast Growth Factor ◽  
Prognostic Marker ◽  
Diagnostic Marker ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth

Abstract Background Gestational diabetes mellitus (GDM) defined as glucose intolerance with onset or first diagnosis during pregnancy. While GDM usually resolves following delivery, it can have long-lasting health consequences, including increased risk for type 2 diabetes (T2DM) and cardiovascular disease (CVD) in the mother, and future obesity, CVD, T2DM, and/or GDM in the child. This contributes to a vicious intergenerational cycle of obesity and diabetes that impacts the health of the population as a whole. Fibroblast growth factor 21 (FGF21) is a hormone that is expressed predominantly in the liver, but also in other metabolically active tissues such as pancreas, skeletal muscle and adipose tissue. An elevated FGF21 level is also an independent predictor of T2DM. GDM and T2DM are proposed to have similar underlying pathophysiologies, raising the question of whether a similar relationship exists between FGF21 and GDM as it does with T2DM. Objectives assess the role of Fibroblast growth factor 21 (FGF-21) as a prognostic marker for maternal and fetal complications in patients with gestational diabetes mellitus (GDM). Patients and Methods A case control study that was conducted on 50 patients diagnosed with Gestational Diabetes Mellitus and 50 control subjects at Diabetes and Obstetrics outpatient clinic and inpatient ward at Ain Shams university hospitals in the period between December 2018 and July 2019. Patients diagnosed with gestational diabetes mellitus (GDM) at 24-28 weeks of gestation were included in this study. Results FGF 21 levels varied significantly with blood sugar values where higher levels of FGF 21 levels were found in patients with GDM with study results showing that FGF 21 can be used as a diagnostic marker for GDM at levels above 121 pg/ml with sensitivity 84% and specificity 92%. Conclusion FGF 21 can be used as a diagnostic marker for gestational diabetes. Further studies needed for better correlation between FGF 21 levels during pregnancy and maternal outcome.

scholarly journals miR-657 Promotes Macrophage Polarization toward M1 by Targeting FAM46C in Gestational Diabetes Mellitus

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Pingping Wang ◽  
Zengfang Wang ◽  
Guojie Liu ◽  
Chengwen Jin ◽  
Quan Zhang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Macrophage Polarization ◽  
Vital Role ◽  
Luciferase Reporter ◽  
M2 Macrophage ◽  
And Migration

MicroRNA (miRNA) has been widely suggested to play a vital role of in the pathogenesis of gestational diabetes mellitus (GDM). We have previously demonstrated that miR-657 can regulate macrophage inflammatory response in GDM. However, the role of miR-657 on M1/M2 macrophage polarization in GDM pathogenesis is not clear yet. This study is aimed at elucidating this issue and identifying novel potential GDM therapeutic targets based on miRNA network. miR-657 is found to be upregulated in placental macrophages demonstrated by real-time PCR, which can enhance macrophage proliferation and migration in vitro. Luciferase reporter assay shows the evidence that FAM46C is a target of miR-657. In addition, miR-657 can promote macrophage polarization toward the M1 phenotype by downregulating FAM46C in macrophages. The present study strongly suggests miR-657 is involved in GDM pathogenesis by regulating macrophage proliferation, migration, and polarization via targeting FAM46C. miR-657/FAM46C may serve as promising targets for GDM diagnosis and treatment.

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