Gestational diabetes reduces adenosine transport in human placental microvascular endothelium, an effect reversed by insulin

Salomon, Carlos, Westermeier, Francisco, Puebla, Carlos, Arroyo, Pablo, Guzman-Gutierrez, Enrique, Pardo, Fabian, Leiva, Andrea, Casanello, Paola and Sobrevia, Luis (2012) Gestational diabetes reduces adenosine transport in human placental microvascular endothelium, an effect reversed by insulin. PLoS ONE, 7 7: e40578.1-e40578.14. doi:10.1371/journal.pone.0040578


Author Salomon, Carlos
Westermeier, Francisco
Puebla, Carlos
Arroyo, Pablo
Guzman-Gutierrez, Enrique
Pardo, Fabian
Leiva, Andrea
Casanello, Paola
Sobrevia, Luis
Title Gestational diabetes reduces adenosine transport in human placental microvascular endothelium, an effect reversed by insulin
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2012-07-12
Year available 2012
Sub-type Article (original research)
DOI 10.1371/journal.pone.0040578
Open Access Status DOI
Volume 7
Issue 7
Start page e40578.1
End page e40578.14
Total pages 14
Place of publication San Francisco United States
Publisher Public Library of Science (PLoS)
Language eng
Formatted abstract
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 (p42/44mapk) 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 p42/44mapk/Akt ratios ('metabolic phenotype') were lower in GDM. Insulin reversed GDM-reduced hENT2 expression/activity, IR-A/IR-B mRNA expression and p42/44mapk/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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Centre for Clinical Research Publications
 
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