Cell signalling-mediating insulin increase of mRNA expression for cationic amino acid transporters-1 and-2 and membrane hyperpolarization in human umbilical vein endothelial cells

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dc.contributor.authorGonzález, M
dc.contributor.authorFlores, C
dc.contributor.authorPearson, JD
dc.contributor.authorCasanello, P
dc.contributor.authorSobrevia, L
dc.date.accessioned2025-01-21T01:07:49Z
dc.date.available2025-01-21T01:07:49Z
dc.date.issued2004
dc.description.abstractInsulin induces vasodilatation in human subjects and increases L-arginine transport and NO synthesis in human umbilical vein endothelial cells (HUVEC). Cell signalling events associated with insulin effects on activity and mRNA expression of the human cationic amino acid transporters 1 (hCAT-1) and 2B (hCAT-2B) are unknown. L-Arginine transport and eNOS activity were determined in HUVEC exposed to insulin. mRNA levels for hCAT-1, hCAT-2B and eNOS were quantitated by real time RTPCR and endothelial NO synthase (eNOS) protein was identified by Western blot analysis. Intracellular Ca2+, L-arginine and L-citrulline levels, L-[H-3]citrulline formation from L-[H-3]arginine, cGMP formation, nitrite level, ATP release and membrane potential were determined. Insulin increased L-arginine transport and the mRNA levels for hCAT-1 and hCAT-2B and eNOS expression and activity. Insulin also induced membrane hyperpolarization and increased intracellular Ca2+, L-[H-3]citrulline, cGMP and nitrite formation. Insulin-mediated stimulation of the L-arginine/NO pathway is thus associated with increased hCAT-1 and hCAT-2B mRNA, and eNOS expression, via mechanisms involving membrane hyperpolarization, mitogen-activated protein kinases p42 and p44, phosphatidylinositol 3-kinase, NO and protein kinase C. We have characterized a cell signalling pathway by which hyper-insulinaemia could lead to vasodilatation in human subjects, and which could have implications in patients in whom plasma insulin levels are altered, such as in diabetes mellitus.
dc.fuente.origenWOS
dc.identifier.issn0031-6768
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/96384
dc.identifier.wosidWOS:000222991100004
dc.issue.numero4
dc.language.isoen
dc.pagina.final394
dc.pagina.inicio383
dc.revistaPflugers archiv-european journal of physiology
dc.rightsacceso restringido
dc.subjecthuman
dc.subjectinsulin
dc.subjectendothelium
dc.subjectglucose
dc.subjectumbilical
dc.subjectvein
dc.subjectarginine
dc.subjectnitric oxide
dc.subjectdiabetes
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleCell signalling-mediating insulin increase of mRNA expression for cationic amino acid transporters-1 and-2 and membrane hyperpolarization in human umbilical vein endothelial cells
dc.typeartículo
dc.volumen448
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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