PMID- 29104874 OWN - NLM STAT- MEDLINE DCOM- 20180709 LR - 20211204 IS - 2314-6753 (Electronic) IS - 2314-6745 (Print) VI - 2017 DP - 2017 TI - Akt/mTOR Role in Human Foetoplacental Vascular Insulin Resistance in Diseases of Pregnancy. PG - 5947859 LID - 10.1155/2017/5947859 [doi] LID - 5947859 AB - 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. FAU - Villalobos-Labra, Roberto AU - Villalobos-Labra R AUID- ORCID: 0000-0002-9638-9721 AD - Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Catolica de Chile, 8330024 Santiago, Chile. FAU - Silva, Luis AU - Silva L AUID- ORCID: 0000-0002-2883-378X AD - Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Catolica de Chile, 8330024 Santiago, Chile. AD - Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen (UMCG), 9700 RB Groningen, Netherlands. FAU - Subiabre, Mario AU - Subiabre M AUID- ORCID: 0000-0002-1280-9128 AD - Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Catolica de Chile, 8330024 Santiago, Chile. FAU - Araos, Joaquin AU - Araos J AUID- ORCID: 0000-0002-0901-7672 AD - Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Catolica de Chile, 8330024 Santiago, Chile. FAU - Salsoso, Rocio AU - Salsoso R AUID- ORCID: 0000-0002-8218-1882 AD - Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Catolica de Chile, 8330024 Santiago, Chile. AD - Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Seville, Spain. FAU - Fuenzalida, Barbara AU - Fuenzalida B AUID- ORCID: 0000-0002-5128-570X AD - Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Catolica de Chile, 8330024 Santiago, Chile. FAU - Saez, Tamara AU - Saez T AD - Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Catolica de Chile, 8330024 Santiago, Chile. AD - Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen (UMCG), 9700 RB Groningen, Netherlands. FAU - Toledo, Fernando AU - Toledo F AD - Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Catolica de Chile, 8330024 Santiago, Chile. AD - Department of Basic Sciences, Faculty of Sciences, Universidad del Bio-Bio, 3780000 Chillan, Chile. FAU - Gonzalez, Marcelo AU - Gonzalez M AD - Vascular Physiology Laboratory, Department of Physiology, Faculty of Biological Sciences, Universidad de Concepcion, 4070386 Concepcion, Chile. FAU - Quezada, Claudia AU - Quezada C AD - Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, 5110566 Valdivia, Chile. FAU - Pardo, Fabian AU - Pardo F AD - Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Catolica de Chile, 8330024 Santiago, Chile. AD - Metabolic Diseases Research Laboratory, Center of Research, Development and Innovation in Health-Aconcagua Valley, School of Medicine, Faculty of Medicine, Universidad de Valparaiso, San Felipe Campus, 2172972 San Felipe, Chile. FAU - Chiarello, Delia I AU - Chiarello DI AUID- ORCID: 0000-0002-1530-0458 AD - Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Catolica de Chile, 8330024 Santiago, Chile. FAU - Leiva, Andrea AU - Leiva A AD - Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Catolica de Chile, 8330024 Santiago, Chile. FAU - Sobrevia, Luis AU - Sobrevia L AUID- ORCID: 0000-0001-5802-2243 AD - Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Catolica de Chile, 8330024 Santiago, Chile. AD - Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Seville, Spain. AD - University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, Brisbane, QLD 4029, Australia. LA - eng PT - Journal Article PT - Review DEP - 20170914 PL - England TA - J Diabetes Res JT - Journal of diabetes research JID - 101605237 RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Diabetes, Gestational/*metabolism MH - Female MH - Humans MH - Insulin Resistance/*physiology MH - Pre-Eclampsia/*metabolism MH - Pregnancy MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Signal Transduction/physiology MH - TOR Serine-Threonine Kinases/*metabolism PMC - PMC5618766 EDAT- 2017/11/07 06:00 MHDA- 2018/07/10 06:00 PMCR- 2017/09/14 CRDT- 2017/11/07 06:00 PHST- 2017/06/01 00:00 [received] PHST- 2017/08/15 00:00 [accepted] PHST- 2017/11/07 06:00 [entrez] PHST- 2017/11/07 06:00 [pubmed] PHST- 2018/07/10 06:00 [medline] PHST- 2017/09/14 00:00 [pmc-release] AID - 10.1155/2017/5947859 [doi] PST - ppublish SO - J Diabetes Res. 2017;2017:5947859. doi: 10.1155/2017/5947859. Epub 2017 Sep 14.