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Neonates from women with pregestational maternal obesity show reduced umbilical vein endothelial response to insulin.

Abstract：

OBJECTIVE:Pregestational maternal obesity (PGMO) associates with foetoplacental vascular endothelial dysfunction and higher risk for insulin resistance in the neonate. We characterised the PGMO consequences on the insulin response of the human foetoplacental vasculature. METHODS:Umbilical veins were from pregnancies where the mother was with PGMO (body mass index 30-42.3 kg/m2, n = 33) or normal pregestational weight (PGMN) (body mass index 19.5-24.4 kg/m2, n = 21) with total gestational weight gain within the physiological range. Umbilical vein ring segments were mounted in a myograph for isometric force measurements. Primary cultures of human umbilical vein endothelial cells were used in passage 3. Vessel rings and cells were exposed to 1 nmol/L insulin (20 min) in the absence or presence of 100 μmol/L NG-nitro-l-arginine methyl ester (inhibitor of nitric oxide synthase, NOS). RESULTS:Vessel rings from PGMO showed reduced nitric oxide synthase-activity dependent dilation to insulin or calcitonin-gene related peptide compared with PGMN. PGMO associated with higher inhibitor phosphorylation of the insulin receptor substrate 1 (IRS-1) and lower activator phosphorylation of protein kinase B/Akt (Akt). Cells from PGMO also showed lower nitric oxide level and reduced activator serine1177 but increased inhibitor threonine495 phosphorylation of endothelial nitric oxide synthase (eNOS) and saturable transport of l-arginine. HUVECs from PGMO were not responsive to insulin. CONCLUSION:The lack of response to insulin by the foetoplacental endothelium may result from reduced IRS-1/Akt/eNOS signalling in PGMO. These findings may result in higher risk of insulin resistance in neonates to PGMO pregnancies.

journal_name

Placenta

journal_title

Placenta

authors

Villalobos-Labra R,Westermeier F,Pizarro C,Sáez PJ,Toledo F,Pardo F,Kusanovic JP,Mardones F,Poblete JA,Sobrevia L,Farías M

doi

10.1016/j.placenta.2019.07.007

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

35-44

eissn

0143-4004

issn

1532-3102

pii

S0143-4004(19)30517-X

journal_volume

86

pub_type

杂志文章

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