Akt/mTOR Role in Human Foetoplacental Vascular Insulin Resistance in Diseases of Pregnancy
|Author||Villalobos Labra, Roberto
Silva, Luis Felipe
Salsoso Rodríguez, Rocío
Sobrevia Luarte, Luis
|Department||Universidad de Sevilla. Departamento de Fisiología|
|Published in||Journal of Diabetes Research, 5947859, 1-13.|
|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 ...
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.
|Citation||Villalobos Labra, R., Silva, L.F., Subiabre, M., Araos, J., Salsoso Rodríguez, R. y Sobrevia Luarte, L. (2017). Akt/mTOR Role in Human Foetoplacental Vascular Insulin Resistance in Diseases of Pregnancy. Journal of Diabetes Research, 5947859, 1-13.|