Regulation of placental glucose transfer and consumption by fetal glucose production.

We studied ten normoglycemic [maternal glucose (GA) = 70 mg/dL] and six insulin-induced hypoglycemic (GA = 22 mg/dL) pregnant sheep to test the hypothesis that development of fetal glucose production (GPR) could help maintain fetal glucose concentration, limit uteroplacental-fetal glucose transfer (UPGT), and sustain uteroplacental glucose consumption (UPGC). Compared with the normoglycemic group, the hypoglycemic group demonstrated the following values: fetal glucose concentration (Ga) was 9.8 +/- 0.8 mg/dL (51% lower, p less than 0.01), uterine glucose uptake (UtGU) was 16.7 +/- 1.4 mg/min (54% lower, p less than 0.01), UPGT was 3.1 +/- 0.6 mg/min (81% lower, p less than 0.001), and UPGC was 13.6 +/- 1.4 mg/min (30% lower, p less than 0.05). The reduction in UPGC was significantly less (p less than 0.05) than the reductions in UPGT and UtGU. Fetal glucose utilization rate (GUR) was decreased 20% (p less than 0.05) to 3.99 +/- 0.35 mg/min/kg. A further decrease in GUR was prevented by the appearance of fetal GPR of 2.82 +/- 0.32 mg/min/kg (p less than 0.05) compared with negligible GPR in the normoglycemic group. UPGT and UPGC in both groups were not influenced by maternal or fetal insulin infusions as long as Ga did not change; however, fetal glucose infusion that increased Ga increased UPGC in both groups. We conclude that, during chronic maternal hypoglycemia, increased fetal GPR limits the simultaneous decrease in fetal GUR and glucose concentration. By sustaining Ga fetal GPR limits UPGT to a significantly greater extent than UtGU, diverting UtGU to UPGC. Thus, fetal GPR promotes placental as well as fetal metabolic autonomy when the maternal supply of glucose is reduced.