Maternal insulin therapy does not restore foetoplacental endothelial dysfunction in gestational diabetes mellitus
Author
dc.contributor.author
Silva, Luis
Author
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Villalobos Labra, Roberto
Author
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Toledo, Fernando
Author
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Paublo Montenegro, Mario
Author
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López Aceitón, Marcia
Author
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Salsoso, Rocio
Author
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Pardo, Fabián
Author
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Escobar Leiva, Andrea Pamela
Author
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Sobrevia, Luis
Author
dc.contributor.author
Subiabre, Mario
Admission date
dc.date.accessioned
2019-06-17T14:49:34Z
Available date
dc.date.available
2019-06-17T14:49:34Z
Publication date
dc.date.issued
2017
Cita de ítem
dc.identifier.citation
BBA - Molecular Basis of Disease 1863 (2017) 2987–2998
es_ES
Identifier
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09254439
Identifier
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10.1016/j.bbadis.2017.07.022
Identifier
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https://repositorio.uchile.cl/handle/2250/169929
Abstract
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Pregnant women diagnosed with gestational diabetes mellitus subjected to diet (GDMd) that do not reach normal glycaemia are passed to insulin therapy (GDMi). GDMd associates with increased human cationic amino acid transporter 1 (hCAT-1)-mediated transport of L-arginine and nitric oxide synthase (NOS) activity in foetoplacental vasculature, a phenomenon reversed by exogenous insulin. Whether insulin therapy results in reversal of the GDMd effect on the foetoplacental vasculature is unknown. We assayed whether insulin therapy normalizes GDMd-associated foetoplacental endothelial dysfunction. Primary cultures of human umbilical vein endothelial cells (HUVECs) from GDMi pregnancies were used to assay L-arginine transport kinetics, NOS activity, p44/42(mapk) and protein kinase B/Akt activation, and umbilical vein rings reactivity. HUVECs from GDMi or GDMd show increased hCAT-1 expression and maximal transport capacity, NOS activity, and eNOS, and p44/42(mapk), but not Akt activator phosphorylation. Dilation in response to insulin or calcitonin-gene related peptide was impaired in umbilical vein rings from GDMi and GDMd pregnancies. Incubation of HUVECs in vitro with insulin (1 nmol/L) restored hCAT-1 and eNOS expression and activity, and eNOS and p44/42(mapk) activator phosphorylation. Thus, maternal insulin therapy does not seem to reverse GDMd-associated alterations in human foetoplacental vasculature
es_ES
Patrocinador
dc.description.sponsorship
Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT), Chile
1150377
1150344
11150083
Servicio de Salud de Medicina Oriente, Hospital San Juan de Dios, Chile
1938-2016
7th European Community Framework Program
295185
Marie Curie International Research Staff Exchange Scheme