scholarly journals Anti‐Diabetic, Anti‐Inflammatory, and Anti‐Oxidant Effects of Naringenin in an In Vitro Human Model and an In Vivo Murine Model of Gestational Diabetes Mellitus

2019 ◽  
Vol 63 (19) ◽  
pp. 1900224 ◽  
Author(s):  
Caitlyn Nguyen‐Ngo ◽  
Jane C Willcox ◽  
Martha Lappas
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Murine Model ◽  
Human Model ◽  
Anti Oxidant ◽  
Anti Inflammatory

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.

scholarly journals Dynamic Regulation of Lipid Metabolism in the Placenta of in Vitro and in Vivo Models of Gestational Diabetes Mellitus

2022 ◽  
Author(s):  
So Young Kim ◽  
Young Joo Lee ◽  
Sung-Min An ◽  
Min Jae Kim ◽  
Jea Sic Jeong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Lipid Metabolism ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Regulatory Element ◽  
Hormone Sensitive Lipase ◽  
Metabolic Complications ◽  
In Vivo Models

Abstract Background: The purpose of this study was to investigate lipid metabolism in the placenta of Gestational diabetes mellitus (GDM) individuals and to evaluate its effect on the fetus. Methods: We examined the expression of lipogenesis- and lipolysis-related proteins in the in vitro and in vivo GDM placenta models. Results: The levels of sterol regulatory element binding protein-1c (SREBP-1c) were increased, and fat accumulated more during early hyperglycemia, indicating that lipogenesis was stimulated. When hyperglycemia was further extended, lipolysis was activated due to the phosphorylation of hormone-sensitive lipase (HSL) and expression of adipose triglyceride lipase (ATGL). In the animal model of GDM and in the placenta of GDM patients during the extended stage of GDM, the expression of SREBP-1c decreased and the deposition of fat increased. Similar to the results obtained in the in vitro study, lipolysis was enhanced in the animal and human placenta of extended GDM. Conclusion: These results suggest that fat synthesis may be stimulated by lipogenesis in the placenta when the blood glucose level is high. Subsequently, the accumulated fat can be degraded by lipolysis and more fat and its metabolites can be delivered to the fetus when the GDM condition is extended at the late stage of gestation. Imbalanced fat metabolism in the placenta and fetus of GDM patients can cause metabolic complications in the fetus, including fetal macrosomia, obesity, and type 2 diabetes mellitus.

Depletion of gut secretory immunoglobulin A coated Lactobacillus reuteri is associated with gestational diabetes mellitus-related intestinal mucosal barrier damage

2021 ◽  
Author(s):  
Haowen Zhang ◽  
Ce Qi ◽  
Yuning Zhao ◽  
Mengyao Lu ◽  
Xinyue Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Lactobacillus Reuteri ◽  
Immunoglobulin A ◽  
Mucosal Damage ◽  
Secretory Iga ◽  
Mucosal Barrier ◽  
Secretory Immunoglobulin

Gestational diabetes mellitus (GDM) may be related to intestinal mucosal damage and inflammation-induced dysbiosis of secretory IgA (SIgA) coated microbiota. SIgA coated L. reuteri can reduce the level of inflammation of GDM in vitro.

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.

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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