Insulin Restores Gestational Diabetes Mellitus Reduced Adenosine Transport Involving Differential Expression of Insulin Receptor Isoforms in Human Umbilical Vein Endothelium

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dc.contributor.authorWestermeier, Francisco
dc.contributor.authorSalomon, Carlos
dc.contributor.authorGonzalez, Marcelo
dc.contributor.authorPuebla, Carlos
dc.contributor.authorGuzman Gutierrez, Enrique
dc.contributor.authorCifuentes, Fredi
dc.contributor.authorLeiva, Andrea
dc.contributor.authorCasanello, Paola
dc.contributor.authorSobrevia, Luis
dc.date.accessioned2024-01-10T12:06:06Z
dc.date.available2024-01-10T12:06:06Z
dc.date.issued2011
dc.description.abstractOBJECTIVE-To determine whether insulin reverses gestational diabetes mellitus (GDM)-reduced expression and activity of human equilibrative nucleoside transporters 1 (hENT1) in human umbilical vein endothelium cells (HUVECs).
dc.description.abstractRESEARCH DESIGN AND METHODS-Primary cultured HUVECs from full-term normal (n = 44) and diet-treated GDM (n = 44) pregnancies were used. Insulin effect was assayed on hENT1 expression (protein, mRNA, SLC29A1 promoter activity) and activity (initial rates of adenosine transport) as well as endothelial nitric oxide (NO) synthase activity (serine(1177) phosphorylation, L-citrulline formation). Adenosine concentration in culture medium and umbilical vein blood (high-performance liquid chromatography) as well as insulin receptor A and B expression (quantitative PCR) were determined. Reactivity of umbilical vein rings to adenosine and insulin was assayed by wire myography. Experiments were in the absence or presence of L-N-G-nitro-L-arginine methyl ester (L-NAME; NO synthase inhibitor) or ZM-241385 (an A(2A)-adenosine receptor antagonist).
dc.description.abstractRESULTS-Umbilical vein blood adenosine concentration was higher, and the adenosine- and insulin-induced NO/endothelium-dependent umbilical vein relaxation was lower in GDM. Cells from GDM exhibited increased insulin receptor A isoform expression in addition to the reported NO-dependent inhibition of hENT1-adenosine transport and SLC29A1 reporter repression, and increased extracellular concentration of adenosine and NO synthase activity. Insulin reversed all these parameters to values in normal pregnancies, an effect blocked by ZM-241385 and
dc.description.abstractCONCLUSIONS-GDM and normal pregnancy HUVEC phenotypes are differentially responsive to insulin, a phenomenon where insulin acts as protecting factor for endothelial dysfunction characteristic of this syndrome. Abnormal adenosine plasma levels, and potentially A2A-adenosine receptors and insulin receptor A, will play crucial roles in this phenomenon in GDM. Diabetes 60:1677-1687, 2011
dc.description.funderFondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT), Chile
dc.description.funderComision Nacional de Investigacion en Ciencia y Tecnologia (CONICYT), Anillos
dc.description.funderFellowship Apoyo de Tesis CONICYT, Chile
dc.description.funderDireccion de Investigacion
dc.description.funderVicerrectoria Academica (Anillos)
dc.description.funderPontificia Universidad Catolica de Chile, Universidad de Antofagasta, Antofagasta, Chile
dc.description.funderDireccion de Investigacion (DIUC)
dc.description.funderUniversidad de Concepcion, Concepcion, Chile
dc.description.funderCONICYT-PhD (Chile)
dc.description.funderFaculty of Medicine, Pontificia Universidad Catolica de Chile-PhD fellowship
dc.fechaingreso.objetodigital2024-05-22
dc.format.extent11 páginas
dc.fuente.origenWOS
dc.identifier.doi10.2337/db11-0155
dc.identifier.eissn1939-327X
dc.identifier.issn0012-1797
dc.identifier.pubmedidMEDLINE:21515851
dc.identifier.urihttps://doi.org/10.2337/db11-0155
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/76116
dc.identifier.wosidWOS:000291369600005
dc.information.autorucMedicina;Casanello P ;S/I;146772
dc.information.autorucCiencias Biológicas;Gonzalez M ;S/I;132310
dc.information.autorucCiencias Biológicas;Guzman E ;S/I;197588
dc.information.autorucMedicina;Leiva A;S/I;3362
dc.information.autorucCiencias Biológicas;Puebla C ;S/I;124965
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.numero6
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final1687
dc.pagina.inicio1677
dc.publisherAMER DIABETES ASSOC
dc.revistaDIABETES
dc.rightsacceso abierto
dc.subjectL-ARGININE TRANSPORT
dc.subjectNITRIC-OXIDE SYNTHESIS
dc.subjectBIRTH-WEIGHT
dc.subjectCELLS
dc.subjectPREGNANCIES
dc.subjectHYPERGLYCEMIA
dc.subjectRECOMMENDATIONS
dc.subjectDYSFUNCTION
dc.subjectASSOCIATION
dc.subjectRESISTANCE
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleInsulin Restores Gestational Diabetes Mellitus Reduced Adenosine Transport Involving Differential Expression of Insulin Receptor Isoforms in Human Umbilical Vein Endothelium
dc.typeartículo
dc.volumen60
sipa.codpersvinculados146772
sipa.codpersvinculados132310
sipa.codpersvinculados197588
sipa.codpersvinculados3362
sipa.codpersvinculados124965
sipa.codpersvinculados189546
sipa.codpersvinculados1002656
sipa.codpersvinculados181374
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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