Insulin requires normal expression and signaling of insulin receptor A to reverse gestational diabetes-reduced adenosine transport in human umbilical vein endothelium

Faseb Journal

dc.creatorWestermeier, Francisco
dc.creatorSalomon, Carlos
dc.creatorFarias, Marcelo
dc.creatorArroyo, Pablo
dc.creatorFuenzalida, Bárbara
dc.creatorSáez-Gutiérrez, Tamara Andrea
dc.creatorSalsoso-Rodríguez, María Rocío
dc.creatorSanhueza, Carlos
dc.creatorGuzmán-Gutiérrez, Enrique
dc.creatorPardo, Fabián
dc.creatorLeiva, Andrea
dc.creatorSobrevia-Luarte, Luis Alberto
dc.date2019-06-25T21:50:42Z
dc.date2022-07-07T21:48:18Z
dc.date2019-06-25T21:50:42Z
dc.date2022-07-07T21:48:18Z
dc.date2015
dc.date.accessioned2023-08-22T22:36:56Z
dc.date.available2023-08-22T22:36:56Z
dc.identifier1150377
dc.identifier1150377
dc.identifierhttps://hdl.handle.net/10533/236144
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8347685
dc.descriptionReduced adenosine uptake via human equilibrative nucleoside transporter 1 (hENT1) in human umbilical vein endothelial cells (HUVECs) from gestational diabetes mellitus (GDM) is reversed by insulin by restoring hENT1 expression. Insulin receptors A (IR-A) and B (IR-B) are expressed in HUVECs, and GDM results in higher IR-A mRNA expression vs. cells from normal pregnancies. We studied whether the reversal of GDM effects on transport by insulin depends on restoration of IR-A expression. We specifically measured hENT1 expression [mRNA, protein abundance, SLC29A1 (for hENT1) promoter activity] and activity (adenosine transport kinetics) and the role of IR-A/IR-B expression and signaling [total and phosphorylated 42 and 44 kDa mitogen-activated protein kinases (p44/42(mapk)) and Akt] in IR-A, IR-B, and IR-A/B knockdown HUVECs from normal (n = 33) or GDM (n = 33) pregnancies. GDM increases IR-A/IR-B mRNA expression (1.8-fold) and p44/ 42(mapk): Akt activity (2.7-fold) ratios. Insulin reversed GDM-reduced hENT1 expression and maximal transport capacity (V-max/K-m), and GDM-increased IR-A/IR-BmRNA expression and p44/42(mapk): Akt activity ratios to values in normal pregnancies. Insulin's effect was abolished in IR-A or IR-A/B knockdown cells. Thus, insulin requires normal IR-A expression and p44/42(mapk)/Akt signaling to restore GDM-reduced hENT1 expression and activity in HUVECs. This could be a protective mechanism for the placental macrovascular endothelial dysfunction seen in GDM. Keywords. Author Keywords:endothelial dysfunction; human placenta; nucleoside membrane transport
dc.relationinstname: Conicyt
dc.relationreponame: Repositorio Digital RI2.0
dc.relationinfo:eu-repo/grantAgreement//1150377
dc.relationinfo:eu-repo/semantics/dataset/hdl.handle.net/10533/93477
dc.relationhttps://doi.org/10.1096/fj.14-254219
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.titleInsulin requires normal expression and signaling of insulin receptor A to reverse gestational diabetes-reduced adenosine transport in human umbilical vein endothelium
dc.titleFaseb Journal
dc.typeArticulo
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion


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