title: Insulin Is a Key Modulator of Fetoplacental Endothelium Metabolic Disturbances in Gestational Diabetes Mellitus.
abstract: Gestational diabetes mellitus (GDM) is a disease of the mother that associates with altered fetoplacental vascular function. GDM-associated maternal hyperglycaemia result in fetal hyperglycaemia, a condition that leads to fetal hyperinsulinemia and altered L-arginine transport and synthesis of nitric oxide, i.e., endothelial dysfunction. These alterations in the fetoplacental endothelial function are present in women with GDM that were under diet or insulin therapy. Since these women and their newborn show normal glycaemia at term, other factors or conditions could be altered and/or not resolved by restoring normal level of circulating D-glucose. GDM associates with metabolic disturbances, such as abnormal handling of the locally released vasodilator adenosine, and biosynthesis and metabolism of cholesterol lipoproteins, or metabolic diseases resulting in endoplasmic reticulum stress and altered angiogenesis. Insulin acts as a potent modulator of all these phenomena under normal conditions as reported in primary cultures of cells obtained from the human placenta; however, GDM and the role of insulin regarding these alterations in this disease are poorly understood. This review focuses on the potential link between insulin and endoplasmic reticulum stress, hypercholesterolemia, and angiogenesis in GDM in the human fetoplacental vasculature. Based in reports in primary culture placental endothelium we propose that insulin is a factor restoring endothelial function in GDM by reversing ERS, hypercholesterolaemia and angiogenesis to a physiological state involving insulin activation of insulin receptor isoforms and adenosine receptors and metabolism in the human placenta from GDM pregnancies.
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, Pontificia Universidad Católica de ChileSantiago, Chile; Faculty of Medicine and Biomedical Sciences, University of Queensland Centre for Clinical Research, University of QueenslandHerston, QLD, Australia; Department of Physiology, Faculty of Pharmacy, Universidad de SevillaSeville, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Sobrevia
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, Pontificia Universidad Católica de ChileSantiago, Chile; Department of Physiology, Faculty of Pharmacy, Universidad de SevillaSeville, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Salsoso
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, Pontificia Universidad Católica de Chile Santiago, Chile.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Fuenzalida
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, Pontificia Universidad Católica de Chile Santiago, Chile.
authors.forename: Eric
authors.initials: E
authors.lastname: Barros
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, Pontificia Universidad Católica de Chile Santiago, Chile.
authors.forename: Lilian
authors.initials: L
authors.lastname: Toledo
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, Pontificia Universidad Católica de Chile Santiago, Chile.
authors.forename: Luis
authors.initials: L
authors.lastname: Silva
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, Pontificia Universidad Católica de Chile Santiago, Chile.
authors.forename: Carolina
authors.initials: C
authors.lastname: Pizarro
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, Pontificia Universidad Católica de Chile Santiago, Chile.
authors.forename: Mario
authors.initials: M
authors.lastname: Subiabre
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, Pontificia Universidad Católica de Chile Santiago, Chile.
authors.forename: Roberto
authors.initials: R
authors.lastname: Villalobos
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, Pontificia Universidad Católica de Chile Santiago, Chile.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Araos
authors.affiliation: Department of Basic Sciences, Faculty of Sciences, Universidad del Bío-Bío Chillán, Chile.
authors.forename: Fernando
authors.initials: F
authors.lastname: Toledo
authors.affiliation: Vascular Physiology Laboratory, Department of Physiology, Faculty of Biological Sciences, Universidad de ConcepciónConcepción, Chile; Group of Research and Innovation in Vascular Health (GRIVAS-Health)Chillán, Chile.
authors.forename: Marcelo
authors.initials: M
authors.lastname: González
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, Pontificia Universidad Católica de ChileSantiago, Chile; Cellular Signaling and Differentiation Laboratory, Health Sciences Faculty, Universidad San SebastiánSantiago, Chile.
authors.forename: Jaime
authors.initials: J
authors.lastname: Gutiérrez
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, Pontificia Universidad Católica de Chile Santiago, Chile.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farías
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, Pontificia Universidad Católica de Chile Santiago, Chile.
authors.forename: Delia I
authors.initials: DI
authors.lastname: Chiarello
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, Pontificia Universidad Católica de Chile Santiago, Chile.
authors.forename: Fabián
authors.initials: F
authors.lastname: Pardo
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, Pontificia Universidad Católica de Chile Santiago, Chile.
authors.forename: Andrea
authors.initials: A
authors.lastname: Leiva
keywords: angiogenesis; endoplasmic reticulum stress; endothelium; gestational diabetes; insulin; lipids; placenta