Glucose Uptake, Utilization, and Transfer by the Human Placenta as Functions of Maternal Glucose Concentration

Abstract

ABSTRACT. The impact of varying maternal glucose concentrations on glucose uptake, transfer, and metabolism was investigated in the human placenta perfused in vitro. The rates of placental glucose uptake from the maternal perfusate and transfer to the fetal perfusate were significantly correlated with maternal glucose concentration up to 20 mM. Placental glucose utilization was also dependent upon maternal glucose concentration up to 17 mM. Between 3 and 53 mM maternal glucose, lactate production increased 3-fold while no change in oxygen consumption could be demonstrated. Correlatively, glucose storage was shown to increase dramatically above 10 mM maternal glucose. These results suggest that glucose supply to the fetus may be limited in times of maternal hypoglycemia and that placental mechanism(s) may serve to buffer glucose transfer to the fetus in conditions of hyperglycemia. Chronic changes in maternal glycemia (hypo or hyper) are known to alter fetal growth and development (1, 2). In the human, the contribution of the placenta to these perturbations is not fully understood. Although placental utilization and transfer of glucose have been studied for many years (3), data are still scarce. This is mainly due to the fact that the studies have been performed in vitro using different experimental procedures, such as placental tissue slices (4, 5), isolated microvilli (6, 7), or perfused placenta (8, 9). In some of these studies, metabolic characteristics were poorly controlled and the results displayed considerable variability. So far, most of the data concerning placental metabolism has been obtained from studies performed in vivo in the sheep (1 0-12). However, it is difficult to extrapolate the data collected in ruminant epitheliochorial placenta to the hemochorial human placenta. The present study was undertaken to determine whether changes in maternal glucose concentration could modify placental glucose metabolism and to what extent this could affect glucose supply to the fetus. MATERIALS AND METHODSPerfusion technique. Term human placentas were obtained from uncomplicated pregnancies after either vaginal delivery or caesarean section. The perfusion experiments were performed on an isolated lobule according to the method described by Panigel et al. (Sigma, St Louis, MO) concentration in medium perfusing the fetal side was fixed at 2.8 mM. Glucose concentration in medium perfusing the maternal side varied from 2.8 to 53 mM. In some experiments 3-3H-~-glucose (10 mCi/mmol, NEN, Paris, France) was added to arterial maternal perfusate to determine the diffusion rate of glucose.Arterial perfusion fluids were continuously gassed with 95%O2 + 5% C02. Flow rates were monitored with R2 15 A Brooks flowmeters and pressures were measured with mercury manometers (Boulitte, Paris, France) on fetal and maternal circulations. Experimental protocol and sampling procedures. Within 30min after delivery the main fetal artery and vein draining the selected lobule were cannulated. The experiments started 20 min after the onse...

Effects of gestational diabetes on human placental glucose uptake, transfer, and utilisation

“…The release of lactate by the placenta was not affected by maternal glucose concentration. This is consistent with previous perfusion studies which showed that the rate of lactate production was not affected by maternal glucose concentrations ranging from 5.5 to 53 mmol/l [12]. The HPLC results suggest that during the time of the experiment (1.5 h), the pool of glucose used for lactate production is independent of the glucose being transported from the maternal perfusate to the fetal effluent.…”

“…The syncytiotrophoblast, therefore, should have considerable capacity for nutrient buffering. This has been shown to occur at least to some degree for glucose metabolism in non-diabetic human perfused placentae [12].…”

Placental glucose transport and utilisation is altered at term in insulin-treated, gestational-diabetic patients

“…Net glucose utilisation was reduced in both GDM groups compared with non-diabetic control subjects and did not increase markedly with increased maternal glucose concentration. Lactate release from the perfused placenta has previously been measured but the comparison of GDM and normal placentae has not been studied [17]. Placental lactate production by the placenta is a normal, aerobic process and not the result of oxygen deficit [18].…”

Defective insulin signaling in placenta from pregnancies complicated by gestational diabetes mellitus

“…The ubiquitously expressed GLUT-1 isoform is inversely related to extracellular glucose concentration in placenta (17) whereas GLUT-4, which is found to a lesser extent in the placenta, are insulin sensitive GLUTs (18). Studies have demonstrated diminished glucose uptake in placental tissue from individuals with GDM (19)(20)(21)(22) and furthermore, increased expression of GLUT-1 in placenta basal membranes from GDM women in comparison with normal controls (23,24).…”