Effects of fetal insulin infusion on glucose kinetics in pregnant sheep: A compartmental analysis

A three-compartment model, consisting of fetus (F), uteroplacenta, and mother (M) was applied to quantitate the effects of fetal hyperinsulinemia on glucose kinetics in pregnant sheep late in gestation. The approach combines the Fick principle with isotope dilution of differentially labeled glucose isotopes, infused simultaneously to F [U-¹⁴C]- and M [2-³H]glucose. In the basal state, rates of umbilical glucose uptake (8.37 ± 0.98 mg/kg per min) and fetal glucose utilization (7.38 ± 1.13) were equivalent (mean ± SE; n = 12). When fetal insulin was increased from 13.7 ± 2.2 to a plateau of ~ 100 μU/ml, arterial glucose decreased from 18.9 ± 0.8 to a new steady state of ~ 13 mg/dl (P < 0.001). Whereas umbilical glucose uptake increased at 90 min and remained elevated thereafter (P < 0.01), fetal glucose utilization increased only transiently at 60 min by 1.9 ± 0.8 mg/kg per min (26%; P < 0.05) and then returned to base line. Insulin's persistent effect, however, was evident from the sustained doubling of the glucose clearance rate from 39.3 ± 5.9 to 66.6 ± 10.5 ml/kg per min (P < 0.005). No endogenous fetal glucose production was evident throughout the experiments. Maternal glucose production and utilization remained unchanged, although there was a small decline in M glucose concentration and an increase in glucose transfer from M to the uteroplacenta and F, from 33.9 ± 8.1 to 48.1 ± 7.0 mg/min at 60 min (P < 0.01 by paired analysis). We conclude that fetal hyperinsulinemia initially lowers glucose concentration by transiently increasing fetal glucose utilization. Insulin's persistent effect is evident from the sustained increase of glucose clearance and maintenance of a lower glucose plateau despite an increased umbilical glucose uptake.