Gestational diabetes reduces adenosine transport in human placental microvascular endothelium, an effect reversed by insulin.
Gestational diabetes mellitus (GDM) courses with increased fetal plasma adenosine concentration and reduced adenosine transport in placental macrovascular endothelium. Since insulin modulates human equilibrative nucleoside transporters (hENTs) expression/activity, we hypothesize that GDM will alter...
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doaj-96238fd0e8904455b74823a8a86006de2020-11-24T21:35:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0177e4057810.1371/journal.pone.0040578Gestational diabetes reduces adenosine transport in human placental microvascular endothelium, an effect reversed by insulin.Carlos SalomónFrancisco WestermeierCarlos PueblaPablo ArroyoEnrique Guzmán-GutiérrezFabián PardoAndrea LeivaPaola CasanelloLuis SobreviaGestational diabetes mellitus (GDM) courses with increased fetal plasma adenosine concentration and reduced adenosine transport in placental macrovascular endothelium. Since insulin modulates human equilibrative nucleoside transporters (hENTs) expression/activity, we hypothesize that GDM will alter hENT2-mediated transport in human placental microvascular endothelium (hPMEC), and that insulin will restore GDM to a normal phenotype involving insulin receptors A (IR-A) and B (IR-B). GDM effect on hENTs expression and transport activity, and IR-A/IR-B expression and associated cell signalling cascades (p42/44 mitogen-activated protein kinases (p42/44(mapk)) and Akt) role in hPMEC primary cultures was assayed. GDM associates with elevated umbilical whole and vein, but not arteries blood adenosine, and reduced hENTs adenosine transport and expression. IR-A/IR-B mRNA expression and p42/44(mapk)/Akt ratios ('metabolic phenotype') were lower in GDM. Insulin reversed GDM-reduced hENT2 expression/activity, IR-A/IR-B mRNA expression and p42/44(mapk)/Akt ratios to normal pregnancies ('mitogenic phenotype'). It is suggested that insulin effects required IR-A and IR-B expression leading to differential modulation of signalling pathways restoring GDM-metabolic to a normal-mitogenic like phenotype. Insulin could be acting as protecting factor for placental microvascular endothelial dysfunction in GDM.http://europepmc.org/articles/PMC3395671?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Carlos Salomón Francisco Westermeier Carlos Puebla Pablo Arroyo Enrique Guzmán-Gutiérrez Fabián Pardo Andrea Leiva Paola Casanello Luis Sobrevia |
spellingShingle |
Carlos Salomón Francisco Westermeier Carlos Puebla Pablo Arroyo Enrique Guzmán-Gutiérrez Fabián Pardo Andrea Leiva Paola Casanello Luis Sobrevia Gestational diabetes reduces adenosine transport in human placental microvascular endothelium, an effect reversed by insulin. PLoS ONE |
author_facet |
Carlos Salomón Francisco Westermeier Carlos Puebla Pablo Arroyo Enrique Guzmán-Gutiérrez Fabián Pardo Andrea Leiva Paola Casanello Luis Sobrevia |
author_sort |
Carlos Salomón |
title |
Gestational diabetes reduces adenosine transport in human placental microvascular endothelium, an effect reversed by insulin. |
title_short |
Gestational diabetes reduces adenosine transport in human placental microvascular endothelium, an effect reversed by insulin. |
title_full |
Gestational diabetes reduces adenosine transport in human placental microvascular endothelium, an effect reversed by insulin. |
title_fullStr |
Gestational diabetes reduces adenosine transport in human placental microvascular endothelium, an effect reversed by insulin. |
title_full_unstemmed |
Gestational diabetes reduces adenosine transport in human placental microvascular endothelium, an effect reversed by insulin. |
title_sort |
gestational diabetes reduces adenosine transport in human placental microvascular endothelium, an effect reversed by insulin. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
Gestational diabetes mellitus (GDM) courses with increased fetal plasma adenosine concentration and reduced adenosine transport in placental macrovascular endothelium. Since insulin modulates human equilibrative nucleoside transporters (hENTs) expression/activity, we hypothesize that GDM will alter hENT2-mediated transport in human placental microvascular endothelium (hPMEC), and that insulin will restore GDM to a normal phenotype involving insulin receptors A (IR-A) and B (IR-B). GDM effect on hENTs expression and transport activity, and IR-A/IR-B expression and associated cell signalling cascades (p42/44 mitogen-activated protein kinases (p42/44(mapk)) and Akt) role in hPMEC primary cultures was assayed. GDM associates with elevated umbilical whole and vein, but not arteries blood adenosine, and reduced hENTs adenosine transport and expression. IR-A/IR-B mRNA expression and p42/44(mapk)/Akt ratios ('metabolic phenotype') were lower in GDM. Insulin reversed GDM-reduced hENT2 expression/activity, IR-A/IR-B mRNA expression and p42/44(mapk)/Akt ratios to normal pregnancies ('mitogenic phenotype'). It is suggested that insulin effects required IR-A and IR-B expression leading to differential modulation of signalling pathways restoring GDM-metabolic to a normal-mitogenic like phenotype. Insulin could be acting as protecting factor for placental microvascular endothelial dysfunction in GDM. |
url |
http://europepmc.org/articles/PMC3395671?pdf=render |
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