Effect of insulin on transport kinetics of alpha-aminoisobutyric acid in the perfused human placental lobule in vitro.

BACKGROUND: The limited data available on the role of insulin on maternal-fetal transport of amino acids prompted us to undertake this study. METHODS: Transport kinetics of a model amino acid, alpha-aminoisobutyric acid (AIB) was investigated in perfusion of isolated human placental lobules in vitro in non steady-state conditions and the effect of therapeutic dose of insulin was assessed in parallel series of perfusions. National Culture and Tissue Collection medium diluted with Earle's buffered salt solution was used as the perfusate and tritiated water was used as the reference marker for comparison. RESULTS: In five successful perfusions with insulin, differential transport rate indices of AIB for 10, 25, 50, 75 and 90% of efflux fractions in the fetal venous outflow averaged 0.76, 1.03, 1.02, 1.09, 1.04 and 1.03 times those of reference values, respectively. The indices differed significantly than in controls for 10, 25 and 50% efflux fractions, but not in the case of 75 and 90% efflux values. The AIB transport fraction (TF), expressed as percentage of injected maternal dose, averaged 29.4 +/- 5.4% and 38.7 +/- 6.2% of the corresponding reference marker value in control and insulin series, respectively. With regards to the pharmacokinetic transport parameters, the absorption and elimination rates of the amino acid were significantly higher in the study group than in the control. CONCLUSION: We conclude that insulin, in physiological and therapeutic doses, stimulates maternal-fetal AIB transport in vitro, in the perfused human placental lobule.

Kinetics of palmitic acid transport in insulin-dependent diabetic pregnancies: in vitro study.

BACKGROUND: The paucity of data relating to transport kinetics of free fatty acids (FFA) in pregnant diabetic women prompted the undertaking of the present study. METHODS: Transport kinetics of a model FFA, palmitic acid, have been investigated in Type I diabetic pregnancies, using in vitro perfusion of isolated placental lobules. National Cancer Tissue Culture medium diluted with Earle's buffered salt solution was used as the perfusate and control placental lobules were perfused for comparison. RESULTS: In five Type I diabetic women, the palmitic acid transport fraction (TF) averaged 5.6 +/- 0.42% of injected maternal bolus dose, representing 11.8 +/- 2.1% that of tritiated water used as reference. In control perfusions (n = 5), the palmitic acid TF represented 10.2 +/- 1.3% of tritiated water TF. Differential transport rates of palmitic acid for 10, 25, 50, 75 and 90% of efflux in fetal veins differed significantly from the corresponding values for tritiated water in both study and control series. However, palmitic acid transport rates for the various efflux fractions in the two series were not significantly different. For kinetic parameters, such as area under the curve, clearance, elimination constant, time for maximum response, absorption rate and elimination rate, the values for palmitic acid in the diabetic and control series also did not differ significantly. CONCLUSION: Transport kinetics of palmitic acid in Type I human diabetic pregnancies in in vitro conditions do not differ significantly from those observed in normal pregnancies.

Effect of glucose load on the transport kinetics of palmitic acid in the human placenta: an in vitro study.

1. A paucity of data relating to free fatty acid (FFA) transport in the human placenta in non-steady state conditions prompted us to undertake the present study. 2. The transport kinetics of palmitic acid in non-steady state conditions have been investigated in vitro using human perfused placental lobules. The effects of varying glucose concentrations on maternal-foetal transport of the FFA were also investigated to mimic the hyperglycaemic states of human diabetic pregnancies. 3. National Cancer Tissue Culture medium diluted with Earle's buffered salt solution was used as the perfusate. [14C]-Palmitic acid, along with tritiated water as a reference, was injected as a bolus into the maternal arterial perfusate and perfusate samples were collected from the venous outflow for a period of 5 min. 4. The transport fraction (TF) of palmitic acid, expressed as percentage of the injected bolus, averaged 3.45 +/- 0.15% in five perfusions, representing 9.2 +/- 1.3% of the corresponding reference marker TF. Kinetic parameters, as well as TF indices of palmitic acid expressed in relation to the reference substance, did not differ significantly between perfusions with a physiological glucose load and those with hyperglycaemic concentrations of glucose of 27.8 and 55.6 mmol/L. 5. The present study shows that hyperglycaemia per se does not significantly alter palmitic acid transport kinetics in vitro in the human perfused placental lobule.