The effect of insulin on glucose uptake, transfer, and metabolism was investigated in the human placenta perfused in vitro. Insulin concentrations in maternal perfusion medium were varied from 0-1200 microU/ml, whereas the glucose concentration was kept constant in maternal and fetal perfusion media. Despite significant uptake of insulin by the perfused placenta, neither glucose uptake and transfer nor lactate release were significantly modified during a 1-h insulin perfusion. The MCR of insulin by the placenta was 0.29 +/- 0.03 (+/- SEM) ml/min X g at physiological insulin levels. These data suggest that placental glucose transport and metabolism are insensitive to maternal plasma insulin variations and that the low clearance rate of insulin by the placenta is not a major determinant of maternal insulin adjustments during pregnancy.

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...

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