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W W Hay

Publications and source records attributed to W W Hay.

At least 73 records · Page 4Linked to original sources
PubMed1994

Placental supply of energy and protein substrates to the fetus.

Table 1 shows an approximate metabolic balance sheet for the fetal sheep at late gestation. The metabolic balance in humans has not been determined but is estimated to be similar, except for a greater caloric requirement for fat deposition, adding about 33 kcal/kg/day to the total fetal caloric intake (34). The total fetal metabolic rate accounts for about 58% of caloric uptake. This percentage is close to the sum of the measured oxidation percentages of the principal energy substrates; this discrepancy cannot yet be explained.

Acetates↗
PubMed1994

Placental transport of nutrients to the fetus.

The exchange of nutrients between placenta and fetus involves three major mechanisms: (1) direct placental transfer of nutrients from the maternal to the fetal plasma; (2) placental metabolism and consumption of nutrients; (3) placental metabolism of nutrient substrates to alternate substrate forms. Carbohydrate is transported to the fetus as glucose which is taken up from the maternal plasma by the GLUT 1 transporter and transported to the fetus by facilitative diffusion according to concentration-dependent kinetics. Protein is transported to the fetus as amino acids by specific amino acid transporter proteins. Placental lipid transport to the fetus involves direct transporter mediated transfer of certain fatty acids as well as lipid uptake from lipoproteins, metabolic alteration in the placenta, and release into the fetal plasma. Placental size, architecture, developmental and pathological processes, and interaction with the fetus cooperate with transport and metabolic mechanisms to affect placental-fetal nutrient exchange.

Amino Acids↗
PubMed1994

Hyperglycemia-induced hyperinsulinemia decreases maternal and fetal plasma protein C concentration during ovine gestation.

To determine effects of diabetic gestation on plasma concentration of the coagulation regulatory protein, protein C, pregnant ewes were given glucose infusions to raise plasma glucose to twice baseline concentration or insulin infusions to lower glucose concentration to half baseline value. Control animals received no infusions. Concentrations of protein S, factor X, and antithrombin III were determined for comparison. Concentrations of glucose, insulin, and those above were determined thrice weekly for 2-9 wk. Short-term (8-12 h) infusions of glucose or insulin were performed to isolate their effect on concentration of protein C. Results were analyzed using a two-tailed t test, and protein C concentrations were further analyzed using a full linear mixed-effects model. In long-term infusions, hyperglycemia-induced hyperinsulinemia (mean insulin concentration 141 microU/L) exerted negative effects on maternal concentrations of protein C [0.69 U/mL, n (number of samples) = 32, experimental versus 0.97 U/mL, n = 157, control], protein S (0.86 U/mL, n = 31, experimental versus 1.04 U/mL, n = 109, control), and factor X (0.89 U/mL, n = 31, experimental versus 1.04 U/mL, n = 109, control); it exerted no effects on antithrombin III (1.05 U/mL, n = 23, experimental versus 1.04 U/mL, n = 32, control). The fetal lamb did not respond to chronic moderate hyperglycemia (mean 33 mg/dL) with a consistent change in insulin concentration (mean 10 versus 9 microU/mL): no coagulation protein changed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Development of primary culture of ovine fetal hepatocytes for studies of amino acid metabolism and insulinlike growth factors.

We report the development and characterization of a system of primary culture of ovine fetal hepatocytes to aid in the understanding of the cellular regulation of fetal growth and metabolism with emphasis on amino acid metabolism and insulinlike growth factor gene expression and to allow comparison to in vivo studies. Hepatocytes were isolated from late gestation fetal lambs by in situ perfusion and collagenase digestion utilizing occlusion of the ductus venosus to limit intrahepatic shunting. Hepatocytes were cultured in media modified to mimic fetal concentrations of glucose, lactate, and amino acids. Ovine fetal hepatocytes in primary culture maintain the pattern of fetal amino acid production and utilization seen across the fetal liver in vivo. Specifically, there is a net production of serine and a net utilization of glycine. Cultured ovine fetal hepatocytes specifically increase tritiated thymidine incorporation in response to insulin and insulinlike growth factor II (IGF-II). IGF-II mRNA abundance is high and IGF-I mRNA is low in cultured ovine fetal hepatocytes as in the fetal sheep liver in vivo. These data demonstrate the successful isolation of ovine fetal hepatocytes that retain some of the characteristics of the ovine fetal liver while maintained in short-term culture.

Amino Acids↗
PubMed1993

Induction of cytosolic phosphoenolpyruvate carboxykinase in the ovine fetal liver by chronic fetal hypoglycemia and hypoinsulinemia.

Fetal glucose production has been observed in the chronically hypoglycemic, hypoinsulinemic (HH) fetal lamb. The purpose of this study was to test the hypothesis that induction of hepatic gluconeogenic enzymes occurs in this condition. The activities of both mitochondrial and cytosolic phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-diphosphatase, and glucose-6-phosphatase, three key enzymes of gluconeogenesis, were determined in fetal sheep liver from HH lambs and controls (CONT). Pregnant ewes were maintained chronically hypoglycemic by continuous hyperinsulinemic clamps from approximately 80 d of gestational age (53% of gestation) for 6 wk. Fetuses (gestational age: HH = 136 +/- 2.6, CONT = 133 +/- 3.7 d) were maintained chronically hypoglycemic [HH = 0.51 +/- 0.05 versus CONT = 1.22 +/- 0.11 mmol/L (9.2 +/- 1.0 versus 21.9 +/- 11.9 mg/dL)] and hypoinsulinemic (HH = 3.3 +/- 0.6 versus CONT = 12.0 +/- 2.2 microU/mL) and delivered by cesarean section after measurement of fetal glucose production rate. Hepatic cytosolic PEPCK was 6.0 +/- 1.4 nmol/min/mg protein in CONT and 19.7 +/- 2.5 in HH lamb (p < 0.05), whereas mitochondrial PEPCK was not different between the two groups. Neither fructose-1,6-diphosphatase or glucose-6-phosphatase activities nor plasma glucagon levels were different between groups. These results suggest that chronic fetal hypoglycemia and hypoinsulinemia prematurely induce hepatic cytosolic PEPCK in the fetal lamb. The observed fetal glucose production in the HH fetal lamb may be due to gluconeogenesis.

Animals↗
PubMed1993

Ontogeny of insulin effect in fetal sheep.

Compared with fetuses near term, midgestation fetal sheep at about 75 d of gestation have higher weight-specific glucose uptake rates, higher plasma glucose concentrations, lower plasma insulin concentrations, higher red blood cell insulin receptor concentrations and affinity, and a lower proportion of body weight accounted for by potentially insulin-sensitive skeletal muscle. Based on these observations, we measured the net rate of glucose uptake by the fetus from the uteroplacenta under basal and hyperinsulinemic conditions in eight fetal sheep at 76 d of gestation and eight fetal sheep at 132 d of gestation (term approximately 150 d). Hyperinsulinemia (414 +/- 90 pM) in the 76-d fetal sheep decreased plasma glucose concentration by 0.20 +/- 0.03 mM (-13%, p < 0.01) and increased the net rate of glucose uptake (8.4 +/- 2.2 mumol/min/kg, +21.3%, p < 0.05) and glucose clearance (11.4 +/- 2.6 mL/min/kg, +39%, p < 0.01). In the 132-d fetuses, a comparable hyperinsulinemia (306 +/- 36 pM) decreased plasma glucose concentration (-0.31 +/- 0.02 mM, -26%, p < 0.05) and increased glucose clearance (16.7 +/- 1.8 mL/min/kg, +73.6%, p < 0.05) to a greater extent than in the 76-d fetuses (p < 0.05 and p < 0.01, respectively). Net glucose uptake rate increased significantly in the 132-d fetuses (6.7 +/- 1.1 mumol/min/kg, +27.5%, p < 0.05), but not differently from the 76-d fetuses (p = 0.21). These data define brisk and significant effects of insulin on glucose metabolism in fetal sheep, even as early as approximately 50% of gestation. The midgestation fetal sheep, particularly in relation to its larger fractional content of body water and smaller fractional content of insulin-sensitive tissues, demonstrates glucose metabolic responses to insulin at least as great as those that occur near term.

Animals↗
PubMed1993

Effects of fasting, elevated plasma glucose and plasma insulin concentrations on milk secretion in women.

In order to determine whether short term variations in plasma glucose and/or insulin influence milk lactose secretion in women, the effects of fasting and increased blood insulin and glucose on milk volume and composition were studied with glucose clamp methodology in exclusively and partially breast-feeding women. Twenty hours of fasting had no discernable effect on the output of milk or its macronutrient composition. Four hours of increased plasma insulin, studied under conditions where plasma glucose was maintained at the fasting level, had no effect on milk volume, milk glucose concentration, total fat content or lactose secretion rate. Increased plasma glucose, maintained at twice fasting levels for 4 to 6 h, produced a threefold increase in milk glucose concentration but had no significant effect on the rate of lactose synthesis. In partially breast-feeding women producing no more than 200 ml milk per day, a similar degree of hyperglycaemia increased milk glucose more than fourfold but did not significantly increase the milk secretion rate. It is concluded that human milk production is isolated from the homeostatic mechanisms that regulate glucose metabolism in the rest of the body, in part because the lactose synthetase system has a Km for glucose lower than the concentration available in the Golgi compartment.

Adult↗
PubMed1991

Gestational maturation of placental glucose transfer capacity in sheep.

The net transfer rate of glucose to the fetus from the placenta (Rf,up) increases approximately 10-fold over the second half of pregnancy. To examine the mechanism underlying this increase, we measured Rf,up at different glucose concentration gradients between maternal arterial (GA) and umbilical arterial (Ga) glucose and at three fetal ages: midgestation (76.0 +/- 0.6 days, n = 6), late gestation (131.5 +/- 2.1 days, n = 8), and an intermediate age (103.3 +/- 1.9 days, n = 4). The GA -- Ga gradient was varied by changing Ga below and above control values with fetal insulin and glucose infusions, respectively, while GA was kept constant at 70 +/- 2 mg/dl by a glucose clamp procedure. The slope of the line relating Rf,up to GA -- Ga increased from 0.15 to 1.01 dl/min in the 76- to 131.5-day period, while the intercept in the GA -- Ga axis remained approximately constant at 34 mg/dl. This indicates a fivefold increase in the ability of the placenta to supply glucose to the fetus at fixed values of maternal and fetal glucose concentration (placental glucose transfer capacity). Concomitant with this increase, there was a significant (P less than 0.001) decrease in control Ga from 26.7 +/- 1.3 to 20.3 +/- 0.3 mg/dl, leading to a significant increase in the GA -- Ga gradient and an 11-fold increase in control Rf,up (from 1.53 to 16.77 mg/min). We conclude that, in the second half of pregnancy, fetal glucose demand grows much more rapidly than placental glucose transfer capacity and requires a decrease in fetal glucose concentration to balance glucose supply and demand.

Animals↗
PubMed1991

The placenta. Not just a conduit for maternal fuels.

The placenta is a specialized organ of exchange that provides nutrients to and excretes waste products from the fetus. The exchange of nutrients between placenta and fetus involves three major mechanisms: 1) direct transfer of nutrients from the maternal to the fetal plasma, 2) placental consumption of nutrients, and 3) placental conversion of nutrients to alternate substrate forms. Although direct transfer has been considered the primary means by which placental-fetal exchange controls the supply of nutrients to the fetus and thereby fetal metabolism and growth, the considerable metabolic activity of the placenta provides a large and fundamentally important contribution to both the quality and quantity of nutrient substrates supplied to the fetus; e.g., placental O2 and glucose consumption rates approach or even exceed those of brain and tumor tissue. Other placental metabolic activities include glycolysis, gluconeogenesis, glycogenesis, oxidation, protein synthesis, amino acid interconversion, triglyceride synthesis, and chain lengthening or shortening of individual fatty acids. Thus, consideration of the metabolism of the placenta is essential for a more complete understanding of how the placenta regulates nutrient transfer to the fetus, fetal energy balance, and fetal growth.

Amino Acids↗
PubMed1991

Pulse oximetry in neonatal medicine.

The safety, accuracy, reliability, noninvasiveness, and ease of use make pulse oximetry a valuable addition to oxygen monitoring of infants in special care nurseries. Such instruments are less sensitive to changes in peripheral circulation or to edema, making them more reliable in sick, physiologically unstable babies and in chronically ill babies with bronchopulmonary dysplasia. In these infants, rapid and accurate measurements of oxygen saturation with such instruments can promote optimal ventilator and oxygen management. In addition, observation of changes in oxygenation during various aspects of care can help optimize care plans for each infant. Although there remains a need for knowing PO2 in preterm infants, pulse oxygen saturation monitoring adds an important degree of control of oxygen management.

Age Factors↗
PubMed1990

Insulin resistance of hind-limb tissues in vivo in lactating sheep.

1. The effects of varying the plasma insulin concentration by infusion while maintaining euglycaemia by infusion of glucose on nutrient arterio-venous differences across the hind-limb and mammary gland in lactating and non-lactating sheep were investigated. 2. Insulin infusion increased the glucose arterio-venous difference across the hind-limb; this effect of insulin was decreased by lactation, suggesting that lactation induces insulin resistance in skeletal muscle. 3. Lactation increased but insulin infusion decreased the plasma concentrations of acetate, beta-hydroxybutyrate and non-esterified fatty acids. 4. Insulin infusion decreased the arterio-venous differences of acetate and hydroxybutyrate across the hind-limb; this effect of insulin is probably indirect, resulting from the decrease in plasma concentrations of these metabolites. 5. Infusion of insulin had no effect on the glucose arterio-venous difference across the mammary gland, but did decrease the oxygen arterio-venous difference. 6. The results suggest that lactation results in insulin resistance in skeletal muscle, at least with respect to glucose utilization; this should facilitate the preferential utilization of glucose by the mammary gland.

Acetates↗
PubMed1990

The mechanism of stimulation of respiration by fatty acids in isolated hepatocytes.

Addition of fatty acids to isolated hepatocytes raised respiration rate by 92% and raised mitochondrial membrane potential (delta psi m) in situ from 155 to 162 mV suggesting that the increased fuel supply had a greater effect on respiration rate than any increases in processes that consumed mitochondrial protonmotive force (delta p). The relationship between delta psi m and respiration rate was changed by addition of fatty acids or lactate, showing that there was also stimulation of delta p-consuming reactions. In the presence of oligomycin the relationship between delta psi m and respiration rate was unaffected by substrate addition, showing that the kinetics of delta p consumption by the H+ leak across the mitochondrial inner membrane were unchanged. The stimulation of delta p consumers by fatty acids therefore must be in the pathways of ATP synthesis and turnover. Inhibition of several candidate ATP-consuming reactions had little effect on basal or fatty acid-stimulated respiration, and the nature of the ATP turnover reactions in hepatocytes remains speculative. We conclude that fatty acids (and other substrates) stimulate respiration in hepatocytes in two distinct ways. They provide substrate for the electron transport chain, raising delta p and increasing the non-ohmic proton leak across the mitochondrial inner membrane and the rate of oxygen consumption. They also directly stimulate an unidentified delta p-consuming reaction in the cytoplasm. They do not work by uncoupling or by stimulation of intramitochondrial ATP-turnover reactions.

Adenosine Triphosphate↗
PubMed1990

Versatile stable isotope technique for the measurement of amino acids and keto acids: comparison with radioactive isotope and its use in measuring in vivo disposal rates.

Tracer methods using both carbon-13 and -14 have been utilized for determination of ovine fetal amino acid disposal and the results compared in seven animals. We infused [1-13C]leucine simultaneously with [1-14C]leucine into the fetal circulation of pregnant sheep chronically catheterized during late gestation. Radioactive and stable isotope enrichments of leucine (Leu) and stable isotope enrichments of ketoisocaproic acid (KIC) in the umbilical artery and vein and the maternal artery and uterine vein were measured. Stable isotope enrichments and concentrations of both Leu and KIC were determined from a single 0.2-ml sample by the use of internal standards and electron ionization GC/MS analysis after a simple isolation and derivatization procedure. The KIC/Leu enrichment ratio was measured for the first time in fetal arterial plasma and was 0.66 +/- 0.05 (SE). Fetal leucine disposal rate was 9.0 +/- 0.5 (SE) micron/min/kg. Disposal rates determined by stable isotopes were not different from those determined by radioactive isotopes. The GC/MS stable isotope method provided higher precision in both leucine concentration and enrichment measurements and has been shown to be a general method for the determination of concentration and isotopic enrichment of other amino acids and their corresponding keto acids. Furthermore, this method is ideally suited to clinical studies where large numbers of samples of rather small volume can easily be studied with a short turnaround time.

Amino Acids↗
PubMed1990

Fetal glucose metabolism and oxygen consumption during sustained hypoglycemia.

The present study was conducted to determine the effects of chronic maternal hyperinsulinemia and hypoglycemia on fetal glucose metabolism and fetal growth. Umbilical glucose uptake (UGU), fetal glucose use rate (GUR), and oxidation fraction (GOxF), and fetal endogenous glucose production rate (EGPR) were measured in chronically catheterized, late gestation fetal lambs during moderate (group 2, n = 6) or marked (group 3, n = 6) maternal hypoglycemia induced by chronic maternal insulin infusion. Compared with normoglycemic controls (group 1, n = 10), group 2 moderate hypoglycemic animals had a 38.5% reduction in maternal glucose concentration (GA) with a subsequent 40.3% fall in fetal glucose concentration (Ga), 64% decrease in fetal insulin concentration (Ia), and a 28.9% decrease in UGU. Group 2 fetal GUR fell 13.1%. No significant EGPR was found in group 1 animals; group 2 had a measurable EGPR that was not statistically different from zero due to the wide range of values. In group 3 marked hypoglycemic animals GA was 57.4% lower than control, and Ga, Ia, and UGU were reduced 45.9%, 64%, and 75.7%, respectively. However, GUR fell by only 19.6% due to the appearance of significant fetal EGPR of 2.81 +/- 0.32 mg/min/kg. Fetal GUR in both group 2 and 3 animals were higher than the predicted range (mean +/- 1 SEM) compared with our model of fetal GUR response to changes in glucose and insulin concentrations. Fetal weights at autopsy were lower in groups 2 and 3 than group 1 controls at the same gestational age (P less than .05). We conclude that decreased fetal glucose availability leads to fetal hypoglycemia and hypoinsulinemia, development of fetal endogenous glucose production, and fetal growth retardation.

Animals↗