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

Reduced 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...

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Autores: Westermeier, Francisco, Salomon, Carlos, Farias, Marcelo, Arroyo, Pablo, Fuenzalida, Bárbara, Sáez-Gutiérrez, Tamara Andrea, Salsoso-Rodríguez, María Rocío, Sanhueza, Carlos, Guzmán-Gutiérrez, Enrique, Pardo, Fabián, Leiva, Andrea, Sobrevia-Luarte, Luis Alberto
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:Chile
OAI Identifier:oai:repositorio.anid.cl:10533/236144
Acceso en línea:https://hdl.handle.net/10533/236144
Access Level:acceso abierto
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dc.title.es_CL.fl_str_mv Insulin requires normal expression and signaling of insulin receptor A to reverse gestational diabetes-reduced adenosine transport in human umbilical vein endothelium
dc.title.journal.es_CL.fl_str_mv Faseb Journal
title Insulin requires normal expression and signaling of insulin receptor A to reverse gestational diabetes-reduced adenosine transport in human umbilical vein endothelium
spellingShingle Insulin requires normal expression and signaling of insulin receptor A to reverse gestational diabetes-reduced adenosine transport in human umbilical vein endothelium
Westermeier, Francisco
title_short Insulin requires normal expression and signaling of insulin receptor A to reverse gestational diabetes-reduced adenosine transport in human umbilical vein endothelium
title_full Insulin requires normal expression and signaling of insulin receptor A to reverse gestational diabetes-reduced adenosine transport in human umbilical vein endothelium
title_fullStr Insulin requires normal expression and signaling of insulin receptor A to reverse gestational diabetes-reduced adenosine transport in human umbilical vein endothelium
title_full_unstemmed Insulin requires normal expression and signaling of insulin receptor A to reverse gestational diabetes-reduced adenosine transport in human umbilical vein endothelium
title_sort Insulin requires normal expression and signaling of insulin receptor A to reverse gestational diabetes-reduced adenosine transport in human umbilical vein endothelium
dc.creator.none.fl_str_mv Westermeier, Francisco
Salomon, Carlos
Farias, Marcelo
Arroyo, Pablo
Fuenzalida, Bárbara
Sáez-Gutiérrez, Tamara Andrea
Salsoso-Rodríguez, María Rocío
Sanhueza, Carlos
Guzmán-Gutiérrez, Enrique
Pardo, Fabián
Leiva, Andrea
Sobrevia-Luarte, Luis Alberto
author Westermeier, Francisco
author_facet Westermeier, Francisco
Salomon, Carlos
Farias, Marcelo
Arroyo, Pablo
Fuenzalida, Bárbara
Sáez-Gutiérrez, Tamara Andrea
Salsoso-Rodríguez, María Rocío
Sanhueza, Carlos
Guzmán-Gutiérrez, Enrique
Pardo, Fabián
Leiva, Andrea
Sobrevia-Luarte, Luis Alberto
author_role author
author2 Salomon, Carlos
Farias, Marcelo
Arroyo, Pablo
Fuenzalida, Bárbara
Sáez-Gutiérrez, Tamara Andrea
Salsoso-Rodríguez, María Rocío
Sanhueza, Carlos
Guzmán-Gutiérrez, Enrique
Pardo, Fabián
Leiva, Andrea
Sobrevia-Luarte, Luis Alberto
author2_role author
author
author
author
author
author
author
author
author
author
author
description Reduced 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
publishDate 2015
dc.date.issued.es_CL.fl_str_mv 2015
dc.date.accessioned.none.fl_str_mv 2019-06-25T21:50:42Z
2022-07-07T21:48:18Z
dc.date.available.none.fl_str_mv 2019-06-25T21:50:42Z
2022-07-07T21:48:18Z
dc.type.none.fl_str_mv Articulo
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url https://hdl.handle.net/10533/236144
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dc.relation.doi.es_CL.fl_str_mv 10.1096/fj.14-254219
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dc.relation.uri.none.fl_str_mv https://doi.org/10.1096/fj.14-254219
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dc.rights.*.fl_str_mv Attribution-NonCommercial-NoDerivs 3.0 Chile
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spelling Sobrevia-Luarte, Luis AlbertoLeiva, AndreaPardo, FabiánGuzmán-Gutiérrez, EnriqueSanhueza, CarlosSalsoso-Rodríguez, María RocíoSáez-Gutiérrez, Tamara AndreaFuenzalida, BárbaraArroyo, PabloFarias, MarceloSalomon, CarlosWestermeier, Francisco201510.1096/fj.14-254219https://hdl.handle.net/10533/236144http://purl.org/coar/access_right/c_abf2Insulin requires normal expression and signaling of insulin receptor A to reverse gestational diabetes-reduced adenosine transport in human umbilical vein endotheliumWestermeier, FranciscoSalomon, CarlosFarias, MarceloArroyo, PabloFuenzalida, BárbaraSáez-Gutiérrez, Tamara AndreaSalsoso-Rodríguez, María RocíoSanhueza, CarlosGuzmán-Gutiérrez, EnriquePardo, FabiánLeiva, AndreaSobrevia-Luarte, Luis Alberto2019-06-25T21:50:42Z2022-07-07T21:48:18Z2019-06-25T21:50:42Z2022-07-07T21:48:18Z2015Reduced 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 transport11503771150377virtual::38601-1WOS:000347378600005https://hdl.handle.net/10533/236144instname: Conicytreponame: Repositorio Digital RI2.010.1096/fj.14-254219info:eu-repo/grantAgreement//1150377info:eu-repo/semantics/dataset/hdl.handle.net/10533/93477https://doi.org/10.1096/fj.14-254219info:eu-repo/semantics/openAccessAttribution-NonCommercial-NoDerivs 3.0 Chilehttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/Insulin requires normal expression and signaling of insulin receptor A to reverse gestational diabetes-reduced adenosine transport in human umbilical vein endotheliumFaseb JournalArticuloinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttps://hdl.handle.net/10533/236144http://purl.org/coar/resource_type/c_2df8fbb10678c53b-678c-407b-a716-d547d7b0651fvirtual::38601-10678c53b-678c-407b-a716-d547d7b0651fvirtual::38601-1CC-LICENSElicense_rdfapplication/octet-stream1232https://repositorio.anid.cl/bitstreams/78f159a0-3b0c-43d5-834b-97e34905e6be/downloadf97bcfdf58f3e17b5cec231112dab5b1MD51LICENSElicense.txttext/plain1779https://repositorio.anid.cl/bitstreams/449fc79a-79e9-4ed4-bae3-88735518b8c3/download593a6e7305c66c56041a9f9e15a649c1MD5210533/236144oai:repositorio.anid.cl:10533/2361442023-07-24 16:30:04.131http://creativecommons.org/licenses/by-nc-nd/3.0/cl/info:eu-repo/semantics/openAccesshttps://repositorio.anid.clRepositorio ANIDaletelier@anid.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