Placental-fetal glucose exchange and placental glucose consumption in pregnant sheep

Abstract

To determine the separate effects of changes in fetal glucose and insulin concentrations on uteroplacental glucose transfer (UPGT) and consumption (UPGC) we studied 24 late-gestation pregnant sheep during fetal insulin infusions alone and with simultaneous glucose clamp. Insulin infusion alone increased fetal glucose utilization rate (GUR) by 45% (P less than 0.001), decreasing fetal glucose concentration by 40% (P less than 0.01) and thereby increasing fetal glucose clearance (Clglu) by 150% (P less than 0.001). Maternal-fetal glucose gradient also increased, resulting in a 40% increase (P less than 0.02) in UPGT [measured as umbilical glucose uptake (UGU)] and a 30% decrease (P less than 0.05) in UPGC. Addition of a fetal glucose clamp returned fetal glucose concentration to base line and restored UPGC and UGU to control values with a further 2.25-fold increase in fetal GUR. Clglu did not change, as the increase in GUR was proportional to the increase in fetal glucose concentration. Similarly, in animals receiving an insulin infusion plus glucose clamp throughout, maternal glucose concentration, fetal glucose concentration, UPGC, and UGU did not change, whereas GUR and Clglu increased approximately 1.9-fold. These changes were noted at constant maternal glucose concentration and uterine glucose uptake. Thus variation in fetal glucose concentration rather than fetal insulin concentration directly regulates uteroplacental glucose transfer and consumption, whereas both fetal insulin and glucose affect, in separate ways, fetal glucose utilization and clearance.