AMINO-ACID-TRANSPORT BY THE CULTURED HUMAN PLACENTAL TROPHOBLAST - EFFECT OF INSULIN ON AIB TRANSPORT

Insulin responsiveness in the human placenta is controversial. This study evaluated insulin stimulation of alpha-aminoisobutyric acid (AIB) uptake in cultured human placental trophoblasts. Both Na+-dependent and -independent components of AIB uptake were present in cultured trophoblasts. Na+-dependent AIB uptake was significantly stimulated by insulin in a time-dependent manner, as early as 2 h, with a maximum at 12 h of continuous exposure to hormone. Insulin treatment for 4 h increased both the initial uptake rate and the final intracellular concentration. Stimulation was dependent on insulin concentration, with significant stimulation beginning at 10(-9) M. Insulin treatment increased maximum velocity but not the Michaelis constant. Approximately 75% of basal (unstimulated) AIB uptake was inhibited by 10 mM alpha-methylaminoisobutyric acid (MeAIB). The insulin-stimulated increment above basal AIB uptake was completely inhibited by 10 mM MeAIB. Cycloheximide treatment significantly reduced basal and stimulated AIB uptake, although a significant response to insulin persisted. Na+-dependent AIB uptake was also stimulated by glucagon, dexamethasone, and 8-bromoadenosine 3',5'-cyclic monophosphate, but not by vasopressin. This study further characterizes amino acid uptake by the human placenta and demonstrates that the Na+-dependent component of AIB uptake by the cultured trophoblasts is stimulated by physiological concentrations of insulin.