The relationship of umbilical glucose uptake to uterine blood flow

In 30 experiments performed on 5 pregnant sheep, the rate of glucose transfer from the placenta to fetus via the umbilical circulation was measured while varying uterine blood flow by means of a cuff-type occluder and while maintaining a constant maternal glucose concentration by means of a 'glucose clamp'. Over the range of uterine blood flows obtained, there was no significant effect on the simultaneously measured umbilical blood flow. Fetal glucose uptake and arterial glucose concentration remained normal as the uterine blood flow rate decreased from 600 to 300 ml per min per kg of fetus. At blood flow rates less than 300 ml.min-1.kg-1, the fetal glucose uptake decreased and became negative in one instance while the arterial glucose concentration became variable and markedly increased in 2 animals. This increase in fetal glucose concentration was associated with a decrease in the uterine oxygen delivery rate, a decrease in fetal oxygen content and a decrease in fetal oxygen uptake. These observations support the concept that fetal glucose metabolism is altered by severe hypoxia and demonstrate that there is little effect of uterine blood flow on fetal glucose uptake in the normal physiological range.     

Hindlimb glucose and lactate metabolism during umbilical cord compression and acute hypoxemia in the late-gestation ovine fetus

The metabolic adaptation of the hindlimb in the fetus to a reversible period of adverse intrauterine conditions and, subsequently, to a further episode of acute hypoxemia has been examined. Sixteen sheep fetuses were chronically instrumented with vascular catheters and transit-time flow probes. In nine of these fetuses, umbilical blood flow was reversibly reduced by 30% from baseline for 3 days (umbilical cord compression), while the remaining fetuses acted as sham-operated, age-matched controls. Acute hypoxemia was subsequently induced in all fetuses by reducing maternal fractional inspired oxygen concentration for 1 h. Paired hindlimb arteriovenous blood samples were taken at appropriate intervals during cord compression and acute hypoxemia, and by using femoral blood flow and the Fick principle, substrate delivery, uptake, and output were calculated. Umbilical cord compression reduced blood oxygen content and delivery to the hindlimb and increased hindlimb oxygen extraction and blood glucose and lactate concentration in the fetus. However, hindlimb glucose and oxygen consumption were unaltered during umbilical cord compression. In contrast, hindlimb oxygen delivery and uptake were significantly reduced in all fetuses during subsequent acute hypoxemia, but glucose extraction, oxygen extraction, and hindlimb lactate output significantly increased in sham-operated control fetuses only. Preexposure of the fetus to a temporary period of adverse intrauterine conditions alters the metabolic response of the fetal hindlimb to subsequent acute stress. Additional data suggest that circulating blood lactate may be derived from sources other than the fetal hindlimb under these circumstances. The lack of hindlimb lactate output during acute hypoxemia in umbilical cord-compressed fetuses, despite a significant fall in oxygen delivery to and uptake by the hindlimb, suggests that the fetal hindlimb may not respire anaerobically after exposure to adverse intrauterine conditions. hypoxia     

Current Perspectives on Umbilical Cord Abnormalities Including Blood Flow Parameters Based on Ultrasound Observations

The umbilical cord is a vital structure between the fetus and placenta for the growth and well-being of the fetus. Although the umbilical cord may be the only organ that dies at the beginning of life, it is one of the most important parts of the feta-placental unit and plays a role in determining how life begins. In general, the prenatal examination of the umbilical cord is limited to the observation of the number of vessels and the evaluation of umbilical artery blood flow parameters. Pathologists have done more research on the morphological characteristics of the umbilical cord and linked them to perinatal outcomes. The introduction of advanced imaging technology makes it possible to study the characteristics of fetal umbilical cord from early to late gestation. Many studies have shown that the changes of umbilical cord structure may be related to pathological conditions, such as preeclampsia, fetal growth restriction. Prenatal morphometric umbilical cord characteristics and arterial blood flow parameters in normal and pathologic conditions are discussed in this review.     

Factors affecting gas transfer across the placenta and the oxygen supply to the fetus

The factors that affect placental gas exchange are reviewed, with particular reference to recent measurements of the effect of changes in one or more of these factors on O2 delivery to the fetus and on fetal O2 uptake. Fetal or maternal placental blood flows and blood O2 capacities can be altered by 50% without any major change occurring in fetal O2 uptake: umbilical venous O2 content and fetal O2 delivery fall, but the O2 consumption of the fetus is maintained by increasing the fractional extraction of O2 from the blood. There is evidence that the fetus can also cope with a reduction in blood O2 affinity resulting from replacement of fetal with maternal blood. The critical level of O2 delivery is about 0.6 mmol.min-1.kg-1 in the fetal sheep. When O2 delivery is reduced below this level, by decreasing maternal placental blood flow, raising or lowering fetal haematocrit, decreasing maternal O2 capacity, or decreasing fetal O2 affinity, fetal O2 uptake tends to fall. The resultant tissue hypoxia and inability to maintain oxidative metabolism is reflected in a lowering of arterial blood pH and base excess. Whilst the results of short-term experiments suggest that there exists a large reserve for placental O2 transfer and fetal O2 supply, there is evidence that fetal O2 uptake is more tightly linked to O2 delivery when the latter is reduced for a period of days or weeks. In the long term, restriction of the supply of O2 and nutrients leads to a reduced rate of fetal growth and a reprogramming of tissue development.     

Restriction of placental growth in sheep enhances placental metabolism of fetal beta-endorphin-like immunoreactivity

The opioid polypeptide beta-endorphin is present in fetal blood but it is not clear whether its source is the fetus or the placenta. We therefore measured beta-endorphin in extracts of fetal femoral arterial and umbilical venous blood plasma in sheep by radioimmunoassay to determine whether the fetus or the placenta is the major source of beta-endorphin in the fetal circulation. Chromatographic analysis of extracts of fetal arterial plasma showed that beta-lipotropin and other precursors of beta-endorphin made only a minor contribution to the immunoreactivity detected. Concentrations of immunoreactive beta-endorphin were higher in the femoral artery than in the umbilical vein in fetal sheep between 113 and 128 days of pregnancy. Therefore the placenta removes beta-endorphin or a closely related polypeptide of fetal origin from the umbilical circulation in sheep at this stage of gestation. Acute hypoxaemia and hypoglycaemia increase the concentrations of immunoassayable beta-endorphin in blood plasma of adult and fetal sheep, but little is known about the effects of chronic hypoxaemia or hypoglycaemia on the circulating levels of beta-endorphin and related polypeptides in the fetus. Therefore we also measured immunoreactive beta-endorphin in blood plasma from fetal sheep in which growth retardation in association with restricted placental growth was produced by removal of endometrial caruncles before mating. Intra-uterine growth retardation was accompanied by chronic hypoglycaemia and chronic hypoxaemia in the fetuses. This was not associated with higher concentrations of beta-endorphin-like immunoreactivity in fetal arterial or umbilical venous plasma, but was accompanied by significantly increased placental extraction of fetal immunoreactive beta-endorphin from the umbilical circulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute cord occlusion increases blood ionized magnesium concentration in preterm fetal sheep during maternal magnesium sulfate exposure

This study tested the hypothesis that a pathophysiologic insult to the fetus that decreases pH (umbilical cord occlusion) produces an increase in physiologically active (i.e., ionized) magnesium concentration. Preterm pregnant sheep (n = 7) were instrumented with maternal and fetal catheters and an inflatable vascular occluder was placed around the umbilical cord. After a 2-day recovery period, each ewe received a 4-g loading dose, followed by continuous intravenous infusion of 1 g magnesium sulfate/h. After 48 h, an episode of acute fetal distress was produced by inflation of the umbilical occluder for 10 min. Maternal and fetal arterial blood samples were collected at regular intervals to quantitate ionized magnesium concentration and monitor physiologic status. Magnesium sulfate infusion increased maternal and fetal blood ionized magnesium concentration. In vitro blood analysis demonstrated that there was a linear inverse correlation (r2 = 0.99) between fetal sheep blood pH and ionized magnesium concentration. In vivo, 10 min of umbilical cord occlusion produced an increase in fetal blood ionized magnesium concentration in all animals (P = 0.02) that was temporally related to the decrease in fetal blood pH. Whether this increase in physiologically active magnesium concentration is beneficial (via neuroprotection) or deleterious (via suppression of stress response) to the distressed fetus remains to be determined.     

Umbilical cord occlusion stimulates breathing independent of blood gases and pH

The role of umbilical cord occlusion in the initiation of breathing at birth was investigated by use of 16 unanesthetized fetal sheep near full term. Artificial ventilation with high-frequency oscillation was used to control fetal arterial blood gas tensions. At baseline, PCO2 was maintained at control fetal values and PO2 was elevated to between 25 and 50 Torr. In the first study on six intact and four vagotomized fetuses, arterial PCO2 and PO2 were maintained constant during two 30-min periods of umbilical cord occlusion. Nevertheless, the mean fetal breathing rate increased significantly when the umbilical cord was occluded. In the second study on six intact fetuses, hypercapnia (68 Torr) was imposed by adding CO2 to the ventilation gas. When the umbilical cord was occluded, there was a significantly greater stimulation of breathing (rate, incidence, and amplitude) in response to hypercapnia than in response to hypercapnia alone. During cord occlusion, plasma prostaglandin E2 concentration decreased significantly. Results indicate that cord occlusion stimulates breathing possibly by causing the removal of a placentally produced respiratory inhibitor such as prostaglandin E2 from the circulation.     

Regional blood flow distribution in fetal sheep with intrauterine growth retardation produced by decreased umbilical placental perfusion

To determine the capacity of the fetus to adapt to chronic O2 deficiency produced by decreased placental perfusion in the early development of growth retardation, we embolized the umbilical placental vascular bed of fetal sheep for a period of 9 days. Fetal umbilical placental embolization decreased arterial O2 content by 39%, decreased total placental blood flow by 33%, and produced a 20% reduction in mean fetal body weight. Neither the combined ventricular output nor the regional blood flow distribution was significantly different between the 8 growth-retarded and 7 normally grown fetuses despite the 39% decrease in fetal arterial O2 content. Thus a 33% reduction in total placental blood flow restricts normal fetal growth, but does not exceed the placental circulatory reserve capacity necessary to maintain normal basal metabolic oxygenation. Because the proportion of combined ventricular output to the placenta at rest is decreased in late IUGR fetuses but not in early IUGR fetuses, despite chronic oxygen deficiency, we conclude that the growth retarded fetus maintains a normal regional blood flow distribution until the placental circulatory reserve capacity is depleted.     

Relationship between the appearance of preantral follicles in the fetal ovary of Antarctic minke whales (Balaenoptera bonaerensis) and hormone concentrations in the fetal heart, umbilical cord and maternal blood

The present study aimed to determine the relationship among changes in the number of preantral follicles and concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P4), androstenedione (A) and estradiol-17beta (E2) in the fetal heart, umbilical cord and maternal blood. Primordial follicles had already appeared in a 20 cm fetus and primary follicles were observed in a 50 cm fetus. In a 70 cm fetus, the number of primordial and primary follicles increased rapidly and secondary follicles were present. The concentrations of LH and FSH did not change between 20 cm and 160 cm in fetal length. When the fetal length became > 70 cm, serum levels in the fetus, umbilical cord and mothers, and E2 levels in umbilical cord increased synchronously (p < 0.05). These results showed increases in the number of preantral follicles in the Antarctic minke whale fetal ovary along with fetal growth during the early gestation period. These findings suggest that the change in preantral follicles was associated with changes in the concentration of steroids in early gestation periods. The changes in steroid concentrations in the fetal and umbilical cord blood and the increased number of preantral follicles were coincident at around 70 cm in fetal length, whereas the growth and differentiation of primordial and primary follicles appeared to be independent of FSH and LH.     

The effect of elevation of maternal plasma catecholamines on the fetus and placenta of the pregnant sheep

To study the effects of reduced uterine blood flow on fetal and placental metabolism, adrenaline has been infused at physiological doses (0.5 microgram/min per kg) into the circulation of the pregnant sheep. This gives a reduction of about one third of uterine blood flow at days 120-143 of pregnancy, but causes no significant change in umbilical blood flow. In contrast to the effects of constricting the uterine artery to reduce blood flow to a similar degree, placental oxygen consumption was reduced and that, together with a large increase in lactate production, indicated the placenta became hypoxic. The fetal blood gas status and hence oxygen consumption was not affected significantly. A consistent arterio-venous difference for glucose across the umbilical or uterine circulations was not detected unless the uterine blood flow was comparatively high. Glucose balance across the uterus showed a close linear relationship with uterine blood flow and more particularly with the supply of glucose to the uterus. There was clear evidence for glucose uptake by the placenta and fetus and also glucose output by both. The latter was more common when uterine blood flow was comparatively low or reduced by adrenaline infusion. The results are consistent with the concept that glucose supply has to be maintained to the placenta even at the expense of fetal stores, although lactate can substitute if there is enhanced output because of fetal hypoxia. They indicate that placental mobilisation of glycogen can lead to a net output of glucose to the mother. The manner of communicating to the fetus changes in placental state that occur during maternal adrenaline infusion is not clear. However towards the end of the 60 min infusion, elevation of fetal plasma adrenaline, probably resulting from a breakdown of the placental permeability barrier, may be an important signal.     

Fetal CO2 kinetics

Knowledge of CO2 kinetics in the fetus is important for the design and interpretation of fetal metabolic studies that use carbon-labelled tracers. To study fetal CO2 kinetics, four fetal sheep were infused at constant rate with NaH14CO3 to simulate a constant rate of fetal 14CO2 production from the metabolism of a 14C-labelled substrate. Uterine and umbilical blood flows, and concentrations of 14CO2 and total CO2 in umbilical arterial and venous blood and in uterine arterial and venous blood were measured. During steady state, the excretion of 14CO2 via the umbilical circulation was 99.6 +/- 1.0 (SEM)% of the NaH14CO3 infusion rate. The irreversible disposal rate of CO2 molecules from the fetal CO2 pool was approximately 5 times greater than the metabolic production of CO2 by the fetus. This evidence demonstrates that measurements of fetal 14CO2 excretion via the umbilical circulation can provide an accurate measurement of fetal 14CO2 production and that the exchange rate of CO2 molecules between placenta and fetal blood is much greater than the net rate of excretion of CO2 molecules from fetus to placenta.     

Behavioral activity during prolonged hypoxemia in fetal sheep

Experiments were conducted in unanesthetized, chronically catheterized pregnant sheep to determine the fetal behavioral response to prolonged hypoxemia produced by restricting uterine blood flow. Uterine blood flow was reduced by adjusting a vascular occluder placed around the maternal common internal iliac artery to decrease fetal arterial O2 content from 6.1 +/- 0.3 to 4.1 +/- 0.3 ml/dl for 48 h. Associated with the decrease in fetal O2 content, there was a slight increase in fetal arterial PCO2 and decrease in pH, which were both transient. There was an initial inhibition of both fetal breathing movements and eye movements but no change in the pattern of electrocortical activity. After this initial inhibition there was a return to normal incidence of both fetal breathing movements and eye movements by 16 h of the prolonged hypoxemia. These studies indicate that the chronically catheterized sheep fetus is able to adapt behaviorally to a prolonged decrease in arterial O2 content secondary to the restriction of uterine blood flow.     

Effect of restriction of placental growth on fetal and utero-placental metabolism

The effect of restriction of placental growth on the supply of glucose to the gravid uterus and fetus and on fetal and utero-placental metabolism of glucose and lactate was examined in this study. Endometrial caruncles were removed from 13 sheep (caruncle sheep) prior to mating, which restricted placental growth in the subsequent pregnancy. Half the fetuses of caruncle sheep were small or growth retarded, with the remainder normal in size. After insertion of vascular catheters at 110 days gestation, the caruncle sheep, together with 16 control sheep, were studied between 121 and 130 days of gestation. Glucose delivery to and consumption by the gravid uterus and its contents, both as a total and per kg of tissue mass, was significantly lower in caruncle ewes with small fetuses, although glucose extraction was similar to that in controls. Utero-placental glucose consumption was significantly lower in caruncle ewes carrying small fetuses compared to that in control ewes, both as a total and per kg of placenta. Small caruncle fetuses were hypoxaemic and hypoglycaemic and the lactate concentration in the common umbilical vein was significantly higher than in control sheep. Glucose delivery to and consumption by the fetus was significantly lower in normal-sized and in small caruncle fetuses compared to controls. Fetal glucose consumption per kg of fetus was similar in control and caruncle sheep. Fetal glucose extraction increased as fetal weight decreased. Utero-placental production of lactate was similar in control and caruncle ewes. However, uterine output of lactate decreased as placental weight fell. Utero-placental production of lactate per kg of placenta was significantly higher in caruncle ewes compared to controls and increased as oxygen content in blood from the fetal femoral artery decreased. Fetal lactate consumption per kg of fetus increased as the concentration of lactate in blood from the common umbilical vein increased. It is concluded that intrauterine growth retardation due to restriction of placental growth is associated with a reduced supply of glucose to both the pregnant uterus and fetus and a redistribution of glucose therein to the fetus, both directly as glucose and indirectly as lactate. This reflects the disproportionate maintenance of fetal weight relative to that of the placenta, reduced utero-placental consumption of glucose per kg of placenta, conversion of a greater proportion of that glucose or other substrate(s) to lactate by the placenta and an increase in the fraction of the lactate produced by utero-placental tissues that is secreted into the fetal circulation.     

The effect of carbon dioxide on Doppler flow velocity waveforms in the human fetus.

Twelve healthy pregnant women were studied between 35 to 40 weeks gestation to determine the effect of carbon dioxide on the Doppler flow velocity waveform in the cerebral and umbilical arteries of the human fetus near term. The Resistance index (RI), as an index of vascular resistance, was calculated for the internal carotid and umbilical arteries during a control period while patients breathed room air followed by three randomized 15-30 min study periods with patients breathing either room air, a prepared gas mixture with 2% carbon dioxide, or undergoing controlled hyperventilation as determined by monitoring end-tidal PCO2. The RI of the internal carotid and umbilical arteries both showed a significant inverse relationship to maternal end-tidal PCO2 with a greater negative slope for RI plotted against end-tidal PCO2 in the internal carotid artery (0.0153) than in the umbilical artery (0.0047). The change in the RI as an index of changing vascular resistance, suggests that carbon dioxide is also an important determinant of cerebral blood flow in the human fetus, as previously described for fetal sheep, with a lesser although significant effect on umbilical blood flow.     

Consumption of carbohydrates, amino acids and oxygen across the intestinal circulation in the fetal sheep

Since large volumes of nutrient rich amniotic fluid are swallowed by the fetus, it has been suggested that intestinal digestion and absorption contribute significantly to fetal nutrition. To see if nutrients are being gained across the intestine, we measured blood flow and intestinal arteriovenous concentration differences of glucose, alpha-amino nitrogen, lactate, fructose and oxygen in eleven third trimester fetal sheep with chronically implanted vascular catheters. We found that in fetal blood circulating through the intestine nutrient concentration decreased significantly with arterio-venous concentration differences for glucose of 0.78 +/- 0.21 (SEM) mg/dl (P < 0.002), for alpha-amino nitrogen of 0.52 +/- 0.15 mg/dl (P < 0.005), for lactate of 0.68 +/- 0.24 mg/dl (P < 0.05) and for oxygen of 1.50 +/- 0.08 ml/dl (P < 0.001). Fructose concentration did not change. Blood flow to the fetal intestine averaged 89.92 +/- 7.16 ml/min and the intestine consumed 0.74 +/- 0.24 mg of glucose, 0.43 +/- 0.17 mg of alpha-amino nitrogen, 0.83 +/- 0.28 mg of lactate and 1.37 +/- 0.14 ml of oxygen per minute. Compared to previously published values for the umbilical uptake of nutrients the fetal intestine metabolizes about 4% of the glucose, 6% of the alpha-amino nitrogen, 13% of the lactate and 6% of the oxygen obtained across the umbilical circulation. Intestinal absorption does not appear to serve as a source of simple nutrients for the rest of the fetus, in fact intestinal metabolism extracts significant amounts of nutrients from fetal blood.     

Lactate uptake by the fetal sheep liver

Lactate is produced by the sheep placenta and is an important metabolic substrate for fetal sheep. However, lactate uptake and release by the fetal liver have not been assessed directly. We measured lactate flux across the liver in 16 fetal sheep at 129 (120-138) days gestation that had catheters chronically maintained in the fetal descending aorta, inferior vena cava, right or left hepatic vein, and umbilical vein. Lactate and hemoglobin concentrations and oxygen saturation were measured in blood drawn from all vessels. Umbilical venous, portal venous, and hepatic blood flow were measured by injecting radionuclide-labeled microspheres into the umbilical vein while obtaining a reference sample from the descending aorta. We found net hepatic uptake of lactate (5.0 +/- 4.4 mg/min per 100 g liver). A large quantity of lactate was delivered to the liver (94.2 +/- 78.1 mg/min per 100 g), so that the hepatic extraction of lactate was only 7.7 +/- 6.5%. Hepatic oxygen consumption was 3.18 +/- 3.3 ml/min per 100 g, and the hepatic lactate/oxygen quotient was 2.07 +/- 1.54. There was no significant correlation between hepatic lactate uptake and hepatic lactate or glucose delivery, hepatic oxygen consumption, hepatic blood flow, hepatic glucose flux, total body oxygen consumption, arterial pH, oxygen content, or oxygen saturation. There was, however, a significant correlation between hepatic lactate uptake and umbilical lactate uptake (r = 0.74, P less than 0.005) such that net hepatic lactate uptake was nearly equivalent to that produced across the umbilical-placental circulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glucose and lactate oxidation rates in the fetal lamb

Both glucose and lactate are nutrients of the ovine fetus. Each may be used by the fetus as a fuel for oxidation or as a source of carbon for energy storage and net tissue accretion. The present report describes the oxidation rates of glucose and lactate in vivo for the fetal lamb over a relatively short time period. The fraction of fetal glucose or lactate oxidized was defined as the ratio of 14CO2 excretion across the umbilical circulation to the net entry of [14C]glucose or [14C]lactate into fetal tissues. The fraction of glucose oxidized over a 3-hr study averaged 61.2%, accounting for 2.55 mg X min-1 X kg-1 of glucose oxidized and for 28% of the simultaneous net oxygen uptake. The fraction of lactate oxidized averaged 71.5%, accounting for 4.12 mg X min-1 X kg-1 of lactate oxidized. Oxidation fractions and rates for both glucose and lactate increased with their concentrations in fetal blood suggesting sparing of other fuels for oxidation at higher glucose and lactate concentrations.     

The ontogeny of hemodynamic responses to prolonged umbilical cord occlusion in fetal sheep.

There is evidence that preterm fetuses have blunted chemoreflex-mediated responses to hypoxia. However, the preterm fetus has much lower aerobic requirements than at term, and so moderate hypoxia may not be sufficient to elicit maximal chemoreflex responses; there are only limited quantitative data on the ontogeny of chemoreflex and hemodynamic responses to severe asphyxia. Chronically instrumented fetal sheep at 0.6 (n = 12), 0.7 (n = 12), and 0.85 (n = 8) of gestational age (GA; term = 147 days) were exposed to 30, 25, or 15 min of complete umbilical cord occlusion, respectively. At all ages, occlusion was associated with early onset of bradycardia, profoundly reduced femoral blood flow and conductance, and hypertension. The 0.6-GA fetuses showed a significantly slower and lesser fall in femoral blood flow and conductance compared with the 0.85-GA group, with a correspondingly reduced relative rise in mean arterial blood pressure. As occlusion continued, the initial adaptation was followed by loss of peripheral vasoconstriction and progressive development of hypotension in all groups. The 0.85-GA fetuses showed significantly more sustained reduction in femoral conductance but also more rapid onset of hypotension than either of the younger groups. Electroencephalographic (EEG) activity was suppressed during occlusion in all groups, but the degree of suppression was less at 0.6 GA than at term. In conclusion, the near-midgestation fetus shows attenuated initial (chemoreflex) peripheral vasomotor responses to severe asphyxia compared with more mature fetuses but more sustained hemodynamic adaptation and reduced suppression of EEG activity during continued occlusion of the umbilical cord.     

Effect of insulin on glucose uptake in near-term fetal lambs

Glucose clamp experiments were performed in 27 chronically catheterized, late-gestation fetal lambs in order to measure the effect of fetal insulin concentration on fetal glucose uptake at a constant glucose concentration. Fetal arterial blood glucose concentration was measured over a 30-min control period and then maintained at the control value by a variable glucose infusion into the fetus while insulin was infused at a constant rate into the fetus. Plasma insulin concentration increased from 21 +/- 10 (SD) to 294 +/- 179 (SD) microU X ml-1. The exogenous glucose infusion rate necessary to maintain constant glycemia during the plateau hyperinsulinemia averaged 4.3 +/- 1.6 (SD) mg X min-1 X kg-1. In a subset of 13 animals, total fetal exogenous glucose uptake (FGU; sum of glucose uptake from the placenta via the umbilical circulation plus the steady-state exogenous glucose infusion rate) was measured during the control and hyperinsulinemia period. FGU was directly related to insulin concentration (y = 4.24 + 0.07x) at insulin levels less than 100 microU/ml and increased 132% above control at insulin levels above 100 microU/ml. Hyperinsulinemia did not affect fetal glucose uptake from the placenta via the umbilical circulation. These studies demonstrate that insulin concentration is a major factor controlling glucose uptake in the near-term fetal lamb, and that an increase of fetal insulin does not affect the transport of glucose to the fetus from the placenta.     

Insulin-induced alterations in amino acid metabolism in the fetal lamb

To investigate the role of insulin in modulation of fetal amino acid metabolism, insulin infusions were performed in 10 chronically-catheterized fetal lambs. Fetal insulin infusion caused a dose related fall in the arterial blood concentrations of 13 of 15 amino acids studied as well as a 15-25% decrease in total amino acid concentration. Fetal lambs exhibited a biphasic response of umbilical total amino acid uptake when compared to fetal blood insulin concentration, i.e., at achieved fetal insulin concentrations less than 100 microU/ml, umbilical uptake of 9 specific amino acids as well as summed amino acid uptake from the umbilical circulation were depressed, but at insulin concentrations of 100-350 microU/ml, amino acid uptakes were similar to or above control values. Insulin infusion also caused a drastic diminution in the rate of fetal urea excretion. These findings suggest that insulin acts in the fetus to depress amino acid catabolism, thus altering amino acid extraction and uptake. Depressed protein catabolism with or without enhanced amino acid uptake would have the theoretical effect of stimulation of net protein synthesis with a shift toward use of nonprotein substrates for energy purposes.