RESUMEN
The goal of this research was to investigate movement of sugars across placental plasma membranes. Changes in vesicle volume produced by solute uptake were measured by light scattering. Analysis, performed by fitting of the light scattering data to exponentials, revealed that for certain sugars such as glucose, a rapid component and a second, slower transport process were present. Measurements in the presence of the glucose transport inhibitor phloretin, comparison with the transport of mannitol and analysis of the concentration dependence of the two transport components were used to demonstrate that these two processes are consistent with protein-mediated and lipid-diffusional transport of glucose. Calculation of glucose flux rates using the time constants which define these processes provided values similar to those determined by radioisotopic methods. Glucose, 2-deoxyglucose and galactose were transported both by carrier-mediated and diffusional processes, while mannitol, fructose, ribose and 2-deoxyribose were transported solely by the latter process and not by a protein carrier. The rate of glucose transport across the syncytiotrophoblast basal membrane was slightly greater than that across the microvillous membrane, in contrast to that predicted previously by immunoblotting. In addition, measurements of hexose transmembrane diffusion showed that microvillous and basal transport rates were similar and lower than previously determined. We conclude that this new technique represents a simple and rapid method for investigating sugar transport across placental membranes.
Asunto(s)
Metabolismo de los Hidratos de Carbono , Luz , Placenta/metabolismo , Dispersión de Radiación , Transporte Biológico , Desoxiglucosa/metabolismo , Difusión , Femenino , Fructosa/metabolismo , Galactosa/metabolismo , Glucosa/metabolismo , Glucosa/farmacología , Transportador de Glucosa de Tipo 1 , Humanos , Metabolismo de los Lípidos , Manitol/metabolismo , Intercambio Materno-Fetal , Proteínas de Transporte de Monosacáridos/metabolismo , Embarazo , Rafinosa , Ribosa/metabolismoRESUMEN
This study was designed to investigate the effects of maternal diabetes on glucose transporter expression and glucose transport activity in the human placenta. Syncytiotrophoblast microvillous and basal membranes were prepared from placental tissue obtained at term from pregestational diabetics (White class B) and gestational diabetics controlled either by diet alone (class A1) or by diet and insulin (class A2). These membranes were used to measure GLUT1 glucose transporter expression and D-glucose transport activity. Diabetic groups showed no differences in placental weights or neonatal birth weights compared to controls, although 8 of 25 diabetic fetuses were macrosomic. Glycemic control in the diabetics at term, as assessed by maternal glycosylated hemoglobin, was within normal limits. Basal membrane GLUT1 density was about 2-fold higher in all diabetic groups compared to that in controls, as measured by immunoblotting, whereas no changes were found for the microvillous membranes. D-Glucose uptake across the basal membrane was increased by 40% in the diabetic groups; no changes were observed for the microvillous membrane. These results demonstrate that diabetes causes an increase in basal membrane GLUT1 expression and activity that persists despite a lack of evidence for current or recent maternal hyperglycemia. This suggests the potential for an extended increase in transplacental glucose flux in the absence of maternal hyperglycemia, which may contribute to fetal macrosomia and the other consequences of diabetic pregnancy.