GDM-Induced Macrosomia Is Reversed by Cav-1 via AMPK-Mediated Fatty Acid Transport and GLUT1-Mediated Glucose Transport in Placenta

Guo, Yang; Zhang, Yafang; Wang, Di; Yang, Ruirui; Song, Hui; Han, Linlin; Zhu, Yuexia; Lü, Yanyan; Tan, Yang; Zhan-ping, Shang

doi:10.1371/journal.pone.0170490

Cited by 33 publications

(31 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AMPK activation is lower in the placenta from women with GDM [ 83 , 84 ]. This finding is complemented by high levels of TNF- α and activation of NF- κ B, conditions leading to increased synthesis of mediators of inflammation and impaired insulin action [ 85 , 86 ].…”

Section: Insulin Resistance In Pregnancy Diseasesmentioning

confidence: 99%

Akt/mTOR Role in Human Foetoplacental Vascular Insulin Resistance in Diseases of Pregnancy

Villalobos-Labra

Silva

Subiabre

et al. 2017

Journal of Diabetes Research

View full text Add to dashboard Cite

Insulin resistance is characteristic of pregnancies where the mother shows metabolic alterations, such as preeclampsia (PE) and gestational diabetes mellitus (GDM), or abnormal maternal conditions such as pregestational maternal obesity (PGMO). Insulin signalling includes activation of insulin receptor substrates 1 and 2 (IRS1/2) as well as Src homology 2 domain-containing transforming protein 1, leading to activation of 44 and 42 kDa mitogen-activated protein kinases and protein kinase B/Akt (Akt) signalling cascades in the human foetoplacental vasculature. PE, GDM, and PGMO are abnormal conditions coursing with reduced insulin signalling, but the possibility of the involvement of similar cell signalling mechanisms is not addressed. This review aimed to determine whether reduced insulin signalling in PE, GDM, and PGMO shares a common mechanism in the human foetoplacental vasculature. Insulin resistance in these pathological conditions results from reduced Akt activation mainly due to inhibition of IRS1/2, likely due to the increased activity of the mammalian target of rapamycin (mTOR) resulting from lower activity of adenosine monophosphate kinase. Thus, a defective signalling via Akt/mTOR in response to insulin is a central and common mechanism of insulin resistance in these diseases of pregnancy. In this review, we summarise the cell signalling mechanisms behind the insulin resistance state in PE, GDM, and PGMO focused in the Akt/mTOR signalling pathway in the human foetoplacental endothelium.

show abstract

Section: Insulin Resistance In Pregnancy Diseasesmentioning

confidence: 99%

Akt/mTOR Role in Human Foetoplacental Vascular Insulin Resistance in Diseases of Pregnancy

Villalobos-Labra

Silva

Subiabre

et al. 2017

Journal of Diabetes Research

View full text Add to dashboard Cite

show abstract

“…PRKAA1 is important in glucose metabolism and energy homeostasis; it also interferes with the modulation of biological functions of cells ( 7 ). Previous studies have reported that PRKAA1 is aberrantly expressed in women with GDM and HG-treated vascular endothelial cells ( 8 , 9 ). Regarding potential upstream regulators of PRKAA1, microRNAs (miRNAs) are of interest in research.…”

Section: Introductionmentioning

confidence: 98%

High glucose suppresses the viability and proliferation of HTR‑8/SVneo cells through regulation of the miR‑137/PRKAA1/IL‑6 axis

Peng

2018

Int J Mol Med

View full text Add to dashboard Cite

The aim of the present study was to investigate the mechanism underlying the high glucose (HG)-associated regulation of HTR-8/SVneo cell viability and proliferation during gestational diabetes mellitus (GDM), and to verify the association of microRNA (miR)-137, protein kinase AMP-activated catalytic subunit α1 (PRKAA1) and interlukin-6 (IL-6). miR-137-overexpressing and negative control HTR-8/SVneo cells were established by lentiviral vector infection. Cell Counting Kit-8 and colony formation assays were used to analyze the viability and proliferation of HTR-8/SVneo cells. Reverse transcription-quantitative polymerase chain reaction analysis was used to determine the transcriptional activity of miR-137, PRKAA1 and Il-6, and ELISA and western blot analysis were used to measure the protein levels of IL-6 and PRKAA1, respectively. It was demonstrated that PRKAA1 was decreased in the placental tissues of women with GDM and HG-treated HTR-8/SVneo cells, and that HG upregulated miR-137 and IL-6 in trophoblasts. The overexpression of miR-137 decreased levels of PRKAA1 and increased levels of IL-6 in the HTR-8/SVneo cells. An inhibitor of PRKAA1 promoted the secretion of IL-6, whereas an agonist of PRKAA1 suppressed the production of IL-6. HG treatment and the overexpression of miR-137 reduced the viability and proliferation of HTR-8/SVneo cells in vitro, whereas the activation of PRKAA1 or incubation with IL-6 antibody reversed these effects. Overall, it was concluded that HG suppressed the viability and proliferation of trophoblast cells through the miR-137/PRKAA1/IL-6 axis, which may contribute to pathological changes of placental tissues in GDM.

show abstract

“…The function of CAV1 in the placenta has not been fully elucidated, but it has been implicated in the transport of lipids, glucose homeostasis control, regulation of cell signalling, and membrane trafficking [65][66][67][68][69][70]. CAV1 is also involved in the palmitoylation of ERα, securing it to caveolae/lipid rafts on the cell membrane [71][72][73][74]. During pregnancy, CAV1 has been associated with glucose and fatty acid transport in the placenta by inducing AMPK and reducing the GLUT1 signalling pathway and reversing macrosomia due to gestational diabetes (GD) [74].…”

Section: Discussionmentioning

confidence: 99%

“…CAV1 is also involved in the palmitoylation of ERα, securing it to caveolae/lipid rafts on the cell membrane [71][72][73][74]. During pregnancy, CAV1 has been associated with glucose and fatty acid transport in the placenta by inducing AMPK and reducing the GLUT1 signalling pathway and reversing macrosomia due to gestational diabetes (GD) [74]. Furthermore, CAV1 has been implicated in the mechanism of oedema in preeclampsia (PE) following hypoxia of trophoblasts through the HMGB1/TLR4/CAV-1 pathway [75].…”

Section: Discussionmentioning

confidence: 99%

Involvement of the Endocrine-Disrupting Chemical Bisphenol A (BPA) in Human Placentation

Greca

Kyrou

Pink

et al. 2020

JCM

View full text Add to dashboard Cite

Background: Endocrine-disrupting chemicals (EDCs) are environmental chemicals/toxicants that humans are exposed to, interfering with the action of multiple hormones. Bisphenol A (BPA) is classified as an EDC with xenoestrogenic activity with potentially adverse effects in reproduction. Currently, a significant knowledge gap remains regarding the complete spectrum of BPA-induced effects on the human placenta. As such, the present study examined the effects of physiologically relevant doses of BPA in vitro. Methods: qRT-PCR, Western blotting, immunofluorescence, ELISA, microarray analyses, and bioinformatics have been employed to study the effects of BPA using nonsyncytialised (non-ST) and syncytialised (ST) BeWo cells. Results: Treatment with 3 nM BPA led to an increase in cell number and altered the phosphorylation status of p38, an effect mediated primarily via the membrane-bound estrogen receptor (GPR30). Nonbiased microarray analysis identified 1195 and 477 genes that were differentially regulated in non-ST BeWo cells, whereas in ST BeWo cells, 309 and 158 genes had altered expression when treated with 3 and 10 nM, respectively. Enriched pathway analyses in non-ST BeWo identified a leptin and insulin overlap (3 nM), methylation pathways (10 nM), and differentiation of white and brown adipocytes (common). In the ST model, most significantly enriched were the nuclear factor erythroid 2-related factor 2 (NRF2) pathway (3 nM) and mir-124 predicted interactions with cell cycle and differentiation (10 nM). Conclusion: Collectively, our data offer a new insight regarding BPA effects at the placental level, and provide a potential link with metabolic changes that can have an impact on the developing fetus.

show abstract

GDM-Induced Macrosomia Is Reversed by Cav-1 via AMPK-Mediated Fatty Acid Transport and GLUT1-Mediated Glucose Transport in Placenta

Cited by 33 publications

References 31 publications

Akt/mTOR Role in Human Foetoplacental Vascular Insulin Resistance in Diseases of Pregnancy

Akt/mTOR Role in Human Foetoplacental Vascular Insulin Resistance in Diseases of Pregnancy

High glucose suppresses the viability and proliferation of HTR‑8/SVneo cells through regulation of the miR‑137/PRKAA1/IL‑6 axis

Involvement of the Endocrine-Disrupting Chemical Bisphenol A (BPA) in Human Placentation

Contact Info

Product

Resources

About