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Journal of Diabetes Research
Volume 2017, Article ID 5947859, 13 pages
https://doi.org/10.1155/2017/5947859
Review Article

Akt/mTOR Role in Human Foetoplacental Vascular Insulin Resistance in Diseases of Pregnancy

1Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, 8330024 Santiago, Chile
2Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen (UMCG), 9700 RB Groningen, Netherlands
3Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Seville, Spain
4Department of Basic Sciences, Faculty of Sciences, Universidad del Bío-Bío, 3780000 Chillán, Chile
5Vascular Physiology Laboratory, Department of Physiology, Faculty of Biological Sciences, Universidad de Concepción, 4070386 Concepción, Chile
6Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, 5110566 Valdivia, Chile
7Metabolic Diseases Research Laboratory, Center of Research, Development and Innovation in Health-Aconcagua Valley, School of Medicine, Faculty of Medicine, Universidad de Valparaíso, San Felipe Campus, 2172972 San Felipe, Chile
8University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, Brisbane, QLD 4029, Australia

Correspondence should be addressed to Luis Sobrevia; moc.em@aiverbos

Received 1 June 2017; Accepted 15 August 2017; Published 14 September 2017

Academic Editor: Christian Wadsack

Copyright © 2017 Roberto Villalobos-Labra et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Insulin resistance is characteristic of pregnancies where the mother shows metabolic alterations, such as preeclampsia (PE) and gestational diabetes mellitus (GDM), or abnormal maternal conditions such as pregestational maternal obesity (PGMO). Insulin signalling includes activation of insulin receptor substrates 1 and 2 (IRS1/2) as well as Src homology 2 domain-containing transforming protein 1, leading to activation of 44 and 42 kDa mitogen-activated protein kinases and protein kinase B/Akt (Akt) signalling cascades in the human foetoplacental vasculature. PE, GDM, and PGMO are abnormal conditions coursing with reduced insulin signalling, but the possibility of the involvement of similar cell signalling mechanisms is not addressed. This review aimed to determine whether reduced insulin signalling in PE, GDM, and PGMO shares a common mechanism in the human foetoplacental vasculature. Insulin resistance in these pathological conditions results from reduced Akt activation mainly due to inhibition of IRS1/2, likely due to the increased activity of the mammalian target of rapamycin (mTOR) resulting from lower activity of adenosine monophosphate kinase. Thus, a defective signalling via Akt/mTOR in response to insulin is a central and common mechanism of insulin resistance in these diseases of pregnancy. In this review, we summarise the cell signalling mechanisms behind the insulin resistance state in PE, GDM, and PGMO focused in the Akt/mTOR signalling pathway in the human foetoplacental endothelium.