Regulation of Placental Glucose Transfer and Consumption by Fetal Glucose Production

Abstract

ABSTRACT. 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 (G,) was 9.8 + 0.8 mg/dL (51% lower, p < 0.01), uterine glucose uptake (UtGU) was 16.7 2 1.4 mg/min (54% lower, p < 0.01), UPGT was 3.1 + 0.6 mg/min (81% lower, p < 0.001), and UPGC was 13.6 2 1.4 mg/min (30% lower, p < 0.05). The reduction in UPGC was significantly less ( p < 0.05) than the reductions in UPGT and UtGU. Fetal glucose utilization rate (CUR) was decreased 20% ( p < 0.05) to 3.99 + 0.35 mg/min/kg. A further decrease in CUR was prevented by the appearance of fetal GPR of 2.82 + 0.32 mg/min/kg ( p < 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 G, did not change; however, fetal glucose infusion that increased G, increased UPGC in both groups. We conclude that, during chronic maternal hypoglycemia, increased fetal GPR limits the simultaneous decrease in fetal CUR and glucose concentration. By sustaining G, 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. (Pediatr Res 25:429-434, 1989) Abbreviations GPR, fetal glucose production GA, maternal glucose concentration G,, fetal glucose concentration GIR, glucose infusion rate UGU, umbilical glucose uptake rate (equal to UPGT) UPGT, uteroplacental-fetal glucose transfer UPGC, uteroplacental glucose consumption GUR, glucose utilization rateIn experiments designed to measure the effect of a reduced supply of glucose on fetal glucose metabolism, we observed in Received October 13, 1988; accepted December 28, 1988 fasted, pregnant sheep that, at rates of net fetal glucose uptake less than half of normal, fetal glucose utilization significantly exceeded umbilical glucose uptake (1, 2). Similar preliminary studies showed the progressive development of a positive fetal hepatic vein-umbilical vein glucose concentration difference after three d of fasting-induced maternal and fetal hypoglycemia (3). We interpreted these observations as evidence of GPR by the fetus itself. As previous studies (4, 5) found negligible rates of fetal GPR during maternal normal glycemia, an increased fetal GPR presumably serves to maintain the rate of fetal glucose utilization when maternal glucose supply decreases. It is not obvious, however, how fetal GPR might also affect placental glucose flux. This is an important concern because in recent experiments using fetal glucose and insulin infusions we observed that changes in f...

Materno-foetal exchanges and utilisation of nutrients by the foetus: comparison between species

“…Glucose accounts for a higher proportion of oxygen consumption in the foetal foal (about 40% [33]) or foetal pig (35-40% [34]) than in the foetal lamb (about 30% [35][36][37]) during late gestation. In the case of maternal hypoglycaemia induced by fasting, the contribution of exogenous glucose to foetal requirements is reduced to approximately half of the normal value in sheep [30], its foetal utilisation is decreased, and foetal gluconeogenesis is increased [15,38]. It was even shown by Hodgson et al [39] that 44% of the glucose used by twin foetuses from well-fed ewes was provided by foetal gluconeogenesis.…”

Coordinated changes in hepatic amino acid metabolism and endocrine signals support hepatic glucose production during fetal hypoglycemia

“…Experimental models in pregnant sheep of reduced fetal glucose supply, producing physiological hypoglycemia, include acute hypoglycemia induced by maternal fasting for several days (10,20), prolonged maternal insulin infusions (5,6,17,38,46), or placental insufficiency resulting in IUGR (28,44,45,50). In these studies, increased fetal glucose production rates were identified when fetal glucose utilization rates remained greater than the net rate of glucose uptake from the placenta (19).…”

“…To induce hypoglycemia, a continuous, variable rate infusion of insulin was initiated into the maternal vein (infusate concentration ϭ 1.7 U/ml, Humulin R; Eli Lilly, Indianapolis, IN) in 0.5% BSA (Sigma, St. Louis, MO; in 0.9% NaCl). Maternal arterial plasma glucose was measured at least twice daily and the maternal insulin infusion was adjusted to produce and maintain a 50% reduction relative to the basal period (2,5,6). Fetal metabolic studies described above were repeated on d1 and d4 of hypoglycemia.…”

Induction of Cytosolic Phosphoenolpyruvate Carboxykinase in the Ovine Fetal Liver by Chronic Fetal Hypoglycemia and Hypoinsulinemia

“…The ewes were housed in a room with the temperature controlled between 10 and 20°C. At least two sheep were always housed together for company (6,7 Maternal arterial blood was sampled daily or twice daily for measurement of glucose and insulin concentration. The maternal arterial whole-blood glucose concentrations were used to adjust the insulin infusion rate to achieve a desired arterial whole-blood glucose concentration of approximately 1.4 mmol/L (25 mg/dL), representing an estimated reduction of 50% from normal.…”