Gestational Diabetes Reduces Adenosine Transport in Human Placental Microvascular Endothelium, an Effect Reversed by Insulin

Salomon, C; Westermeier, F; Puebla, C; Arroyo P.; Guzman-Gutierrez, E; Pardo, F; Leiva A.; Casanello, P; Sobrevia, L

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. © 2012 Salomón et al.

Más información

Título según WOS: Gestational Diabetes Reduces Adenosine Transport in Human Placental Microvascular Endothelium, an Effect Reversed by Insulin
Título según SCOPUS: Gestational diabetes reduces adenosine transport in human placental microvascular endothelium, an effect reversed by insulin
Título de la Revista: PLOS ONE
Volumen: 7
Número: 7
Editorial: PUBLIC LIBRARY SCIENCE
Fecha de publicación: 2012
Idioma: English
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-84863733127&partnerID=40&md5=68e44ce4a3a6d182445509683a25dfde
DOI:

10.1371/journal.pone.0040578

Notas: ISI, SCOPUS