Role of placental insufficiency and intrauterine growth restriction on the activation of fetal hepatic glucose production

Glucose is the major fuel for fetal oxidative metabolism. A positive maternal fetal glucose gradient drives glucose across the placenta and is sufficient to meet the demands of the fetus, eliminating the need for endogenous hepatic glucose production (HGP). However, fetuses with intrauterine growth restriction (IUGR) from pregnancies complicated by placental insufficiency have an early activation of HGP. Furthermore, this activated HGP is resistant to suppression by insulin. Here, we present the data demonstrating the activation of HGP in animal models, mostly fetal sheep, and human pregnancies with IUGR. We also discuss potential mechanisms and pathways that may produce and support HGP and hepatic insulin resistance in IUGR fetuses. (C) 2015 Elsevier Ireland Ltd. All rights reserved.