Placental glucose metabolism and its regulation have been investigated in vivo in the rat using the radioactive 2-deoxyglucose technique. In the basal state, placental glucose utilization rates were similar on days 19 and 21 of gestation: 139 +/- 5 and 155 +/- 22 nmol/min/g at maternal blood glucose concentrations of 4.3 +/- 0.1 and 4.2 +/- 0.1 mmol/1. During hyperglycemic clamps, maternal glycemia was raised to 5.5 mmol/liter, a value similar to that during a meal in the rat. In this condition, the rate of placental glucose utilization at 19 days of gestation was increased by 85%. This was due not only to hyperglycemia but also to glucose-induced hyperinsulinemia. Indeed during hyperinsulinemic euglycemic clamps, placental glucose utilization showed a dose-response relationship to insulin (400 and 5000 microU/ml). At 21 days of gestation, placental glucose utilization was not affected by hyperglycemia or by hyperinsulinemia suggesting that in term placenta, glucose metabolism is no longer regulated. When 19-day pregnant rats were fasted for 48 and 96 h, the resulting low blood glucose and plasma insulin concentrations and the high ketone body concentrations induced, respectively, a 40 and 47% reduction of placental glucose utilization. The decrease in placental glucose utilization probably was due to both maternal hypoglycemia and long term adaptation to hyperketonemia. Indeed, the acute hyperketonemia in fed rats did not alter glucose utilization rate in placenta at 19 days of gestation. These data suggest that glucose metabolism in the preterm rat placenta is modulated in vivo by the maternal metabolic environment, particularly by maternal blood glucose and insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)