Insulin-Increased L-Arginine Transport Requires A(2A) Adenosine Receptors Activation in Human Umbilical Vein Endothelium

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dc.contributor.authorGuzman Gutierrez, Enrique
dc.contributor.authorWestermeier, Francisco
dc.contributor.authorSalomon, Carlos
dc.contributor.authorGonzalez, Marcelo
dc.contributor.authorPardo, Fabian
dc.contributor.authorLeiva, Andrea
dc.contributor.authorSobrevia, Luis
dc.date.accessioned2024-01-10T13:49:31Z
dc.date.available2024-01-10T13:49:31Z
dc.date.issued2012
dc.description.abstractAdenosine causes vasodilation of human placenta vasculature by increasing the transport of arginine via cationic amino acid transporters 1 (hCAT-1). This process involves the activation of A(2A) adenosine receptors (A(2A)AR) in human umbilical vein endothelial cells (HUVECs). Insulin increases hCAT-1 activity and expression in HUVECs, and A(2A)AR stimulation increases insulin sensitivity in subjects with insulin resistance. However, whether A(2A)AR plays a role in insulin-mediated increase in L-arginine transport in HUVECs is unknown. To determine this, we first assayed the kinetics of saturable L-arginine transport (1 minute, 37 degrees C) in the absence or presence of nitrobenzylthioinosine (NBTI, 10 mu mol/L, adenosine transport inhibitor) and/or adenosine receptors agonist/antagonists. We also determined hCAT-1 protein and mRNA expression levels (Western blots and quantitative PCR), and SLC7A1 (for hCAT-1) reporter promoter activity. Insulin and NBTI increased the extracellular adenosine concentration, the maximal velocity for L-arginine transport without altering the apparent K-m for L-arginine transport, hCAT-1 protein and mRNA expression levels, and SLC7A1 transcriptional activity. An A2AAR antagonist ZM-241385 blocked these effects. ZM241385 inhibited SLC7A1 reporter transcriptional activity to the same extent in cells transfected with pGL3-hCAT-1(-1606) or pGL3-hCAT-1(-650) constructs in the presence of NBTI + insulin. However, SLC7A1 reporter activity was increased by NBTI only in cells transfected with pGL3-hCAT-1(-1606), and the ZM-241385 sensitive fraction of the NBTI response was similar in the absence or in the presence of insulin. Thus, insulin modulation of hCAT-1 expression and activity requires functional A(2A)AR in HUVECs, a mechanism that may be applicable to diseases associated with fetal insulin resistance, such as gestational diabetes.
dc.description.funderFondo Nacional de Desarrollo Cientifico y Tecnologico
dc.description.funderComision Nacional de Investigacion en Ciencia y Tecnologia [CONICYT], Chile
dc.description.funderCONICYT-PhD (Chile) fellowships
dc.format.extent13 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1371/journal.pone.0041705
dc.identifier.issn1932-6203
dc.identifier.pubmedidMEDLINE:22844517
dc.identifier.urihttps://doi.org/10.1371/journal.pone.0041705
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/79458
dc.identifier.wosidWOS:000306687700143
dc.information.autorucCiencias Biológicas;Guzman E ;S/I;197588
dc.information.autorucMedicina;Leiva A ;S/I;3362
dc.information.autorucMedicina;Pardo F ;S/I;1004392
dc.information.autorucMedicina;Salomon C ;S/I;189546
dc.information.autorucMedicina;Sobrevia L ;S/I;1002656
dc.information.autorucCiencias Biológicas;Westermeier F ;S/I;181374
dc.issue.numero7
dc.language.isoen
dc.nota.accesoSin adjunto
dc.publisherPUBLIC LIBRARY SCIENCE
dc.revistaPLOS ONE
dc.rightsregistro bibliográfico
dc.subjectFACTOR-KAPPA-B
dc.subjectNITRIC-OXIDE
dc.subjectDIFFERENTIAL EXPRESSION
dc.subjectINTERNATIONAL UNION
dc.subjectCELLS
dc.subjectINHIBITION
dc.subjectGLUCOSE
dc.subjectCLASSIFICATION
dc.subjectNOMENCLATURE
dc.subjectPHARMACOLOGY
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleInsulin-Increased L-Arginine Transport Requires A(2A) Adenosine Receptors Activation in Human Umbilical Vein Endothelium
dc.typeartículo
dc.volumen7
sipa.codpersvinculados197588
sipa.codpersvinculados3362
sipa.codpersvinculados1004392
sipa.codpersvinculados189546
sipa.codpersvinculados1002656
sipa.codpersvinculados181374
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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