The effect of hyperinsulinaemia on glucose utilization and oxidation and on oxygen consumption in the fetal lamb

In order to measure the effect of hyperinsulinaemia on fetal glucose metabolism and oxygen consumption, we applied the glucose-clamp technique to experiments in fifteen late-gestation, unstressed, chronically catheterized fetal lambs. In a control period, and immediately thereafter following 2 h of hyperinsulinaemia, we measured fetal glucose utilization and oxidation rates (radioactive tracer methodology) and net fetal uptake rates of exogenous glucose and oxygen uptake rates (Fick principle). During the period of hyperinsulinaemia, fetal glucose concentration was maintained at the average control period value by a variable rate of glucose infusion into the fetus in response to serial 10 min measurements of fetal arterial blood glucose concentration. Hyperinsulinaemia in the fetus (12.12 +/- 1.92 ng X ml-1 (mean +/- S.E.M.) arterial plasma) resulted in a 13% increase in net fetal oxygen uptake rate (0.310 +/- 0.011 to 0.349 +/- 0.012 mmol. min-1 X kg-1), a 106% increase of fetal glucose uptake rate (4.54 +/- 0.43 to 9.35 +/- 0.50 mg X min-1 X kg-1) and an 83% increase of fetal glucose utilization rate (4.94 +/- 0.43 to 9.05 +/- 0.83 mg X min-1 X kg-1). Fetal glucose uptake and utilization rates were not different from each other during the control and the hyperinsulinaemia periods. The fraction of glucose that was oxidized (0.58 +/- 0.05, control; 0.54 +/- 0.05, hyperinsulinaemia) did not change significantly; thus the glucose oxidation rate, the rate of entry of glucose into non-oxidative pathways, and the amount of oxygen used for glucose oxidation all increased in proportion to glucose utilization. These results suggest that insulin promotes the entry of glucose into fetal tissues, thereby increasing fetal glucose utilization and oxidation rates and substituting glucose oxidation for that of other substrates. The insulin-enhanced glucose utilization rate also increases slightly fetal metabolic rate.