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

Villalobos-Labra, Roberto; Westermeier, Francisco; Pizarro, Carolina; Saez, Pablo J.; Toledo, Fernando; Pardo, Fabian; Kusanovic, Juan P; Mardones, Francisco; Poblete, Jose A.; Sobrevia, Luis; Farias, Marcelo

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/m(2), n = 33) or normal pregestational weight (PGMN) (body mass index 19.5-24.4 kg/m(2), 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 mu mol/L N-G-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 serine(1177) but increased inhibitor threonine(495) 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.

Más información

Título según WOS: Neonates from women with pregestational maternal obesity show reduced umbilical vein endothelial response to insulin
Título según SCOPUS: Neonates from women with pregestational maternal obesity show reduced umbilical vein endothelial response to insulin
Título de la Revista: PLACENTA
Volumen: 86
Editorial: W. B. Saunders Co., Ltd.
Fecha de publicación: 2019
Página de inicio: 35
Página final: 44
Idioma: English
DOI:

10.1016/j.placenta.2019.07.007

Notas: ISI, SCOPUS