Lourdes L. Gruca

Glucose turnover and gluconeogenesis in human pregnancy.

The rate of appearance (Ra) of glucose in plasma and the contribution of gluconeogenesis were quantified in normal pregnant women early ( approximately 10 wk) and late ( approximately 34 wk) in gestation. Their data were compared with those of normal nonpregnant women. Glucose Ra was measured using the [U-13C]glucose tracer dilution method. Gluconeogenesis was quantified by the appearance of 2H on carbon 5 and 6 of glucose after deuterium labeling of body water pool. Weight-specific glucose Ra was unchanged during pregnancy (nonpregnant, 1.89+/-0.24; first trimester, 2.05+/-0.21; and third trimester 2.17+/-0.28 mg/kg.min, mean+/-SD), while total glucose Ra was significantly increased (early, 133.5+/-7.2; late, 162.6+/-16.4 mg/min; P = 0.005). The fractional contribution of gluconeogenesis via pyruvate measured by 2H enrichment on C-6 of glucose (45-61%), and of total gluconeogenesis quantified from 2H enrichment on C-5 of glucose (i.e. , including glycerol [68-85%]) was not significantly different between pregnant and nonpregnant women. Inasmuch as total glucose Ra was significantly increased, total gluconeogenesis was also increased in pregnancy (early pregnancy, 94.7+/-15.9 mg/min; late pregnancy, 122.7+/-9.3 mg/min; P = 0.003). These data demonstrate the ability of the mother to adapt to the increasing fetal demands for glucose with advancing gestation. The mechanism for this unique quantitative adjustment to the fetal demands remains undefined.

Relation between transamination of branched-chain amino acids and urea synthesis: evidence from human pregnancy

Protein and nitrogen (N) accretion by the mother is a major adaptive response to pregnancy in humans and animals to meet the demands of the growing conceptus. Quantitative changes in whole body N metabolism were examined during normal pregnancy by measuring the rates of leucine N (QN) and carbon (QC) kinetics with the use of [1-13C,15N]leucine. Rate of synthesis of urea was measured by [15N2]urea tracer. Pregnancy-related change in total body water was quantified by H2[18O] dilution, and respiratory calorimetry was performed to quantify substrate oxidation. A significant decrease in the rate of urea synthesis was evident in the 1st trimester (nonpregnant 4.69 +/- 1.14 vs. pregnant 3.44 +/- 1.11 micromol . kg-1 . min-1; means +/- SD, P < 0.05). The lower rate of urea synthesis was sustained through the 2nd and 3rd trimesters. QN was also lower in the 1st trimester during fasting; however, it reached a significant level only in the 3rd trimester (nonpregnant 166 +/- 35 vs. 3rd trimester 135 +/- 16 micromol . kg-1 . h-1; P < 0.05). There was no significant change in QC during pregnancy. A significant decrease in the rate of transamination of leucine was evident in the 3rd trimester both during fasting and in response to nutrient administration (P < 0.05). The rate of deamination of leucine was correlated with the rate of urea synthesis during fasting (r = 0.59, P = 0.001) and during feeding (r = 0.407, P = 0. 01). These data show that pregnancy-related adaptations in maternal N metabolism are evident early in gestation before any significant increase in fetal N accretion. It is speculated that the lower transamination of branched-chain amino acids may be due to decreased availability of N acceptors such as alpha-ketoglutarate as a consequence of resistance to insulin action evident in pregnancy.Protein and nitrogen (N) accretion by the mother is a major adaptive response to pregnancy in humans and animals to meet the demands of the growing conceptus. Quantitative changes in whole body N metabolism were examined during normal pregnancy by measuring the rates of leucine N ( Q N) and carbon ( Q C) kinetics with the use of [1-13C,15N]leucine. Rate of synthesis of urea was measured by [15N2]urea tracer. Pregnancy-related change in total body water was quantified by H2[18O] dilution, and respiratory calorimetry was performed to quantify substrate oxidation. A significant decrease in the rate of urea synthesis was evident in the 1st trimester (nonpregnant 4.69 ± 1.14 vs. pregnant 3.44 ± 1.11 μmol ⋅ kg-1 ⋅ min-1; means ± SD, P < 0.05). The lower rate of urea synthesis was sustained through the 2nd and 3rd trimesters. Q Nwas also lower in the 1st trimester during fasting; however, it reached a significant level only in the 3rd trimester (nonpregnant 166 ± 35 vs. 3rd trimester 135 ± 16 μmol ⋅ kg-1 ⋅ h-1; P < 0.05). There was no significant change in Q Cduring pregnancy. A significant decrease in the rate of transamination of leucine was evident in the 3rd trimester both during fasting and in response to nutrient administration ( P< 0.05). The rate of deamination of leucine was correlated with the rate of urea synthesis during fasting ( r = 0.59, P = 0.001) and during feeding ( r = 0.407, P = 0.01). These data show that pregnancy-related adaptations in maternal N metabolism are evident early in gestation before any significant increase in fetal N accretion. It is speculated that the lower transamination of branched-chain amino acids may be due to decreased availability of N acceptors such as α-ketoglutarate as a consequence of resistance to insulin action evident in pregnancy.

Amino acids, glutamine, and protein metabolism in very low birth weight infants

Glutamine has been proposed to be conditionally essential for premature infants, and the currently used parenteral nutrient mixtures do not contain glutamine. De novo glutamine synthesis (DGln) is linked to inflow of carbon into and out of the tricarboxylic acid (TCA) cycle. We hypothesized that a higher supply of parenteral amino acids by increasing the influx of amino acid carbon into the TCA cycle will enhance the rate of DGln. Very low birth weight infants were randomized to receive parenteral amino acids either 1.5 g/kg/d for 20 h followed by 3.0 g/kg/d for 5 h (AA1.5) or 3.0 g/kg/d for 20 h followed by 1.5 g/kg/d for 5 h (AA3.0). A third group of babies received amino acids 1.5 g/kg/d for 20 h followed by 3.0 g/kg/d for 20 h (AA-Ext). Glutamine and protein/nitrogen kinetics were examined using [5-15N]glutamine, [2H5]phenylalanine, [1-13C,15N]leucine, and [15N2]urea tracers. An acute increase in parenteral amino acid infusion for 5 h (AA1.5) resulted in decrease in rate of appearance (Ra) of phenylalanine and urea, but had no effect on glutamine Ra. Infusion of amino acids at 3.0 g/kg/d for 20 h resulted in increase in DGln, leucine transamination, and urea synthesis, but had no effect on Ra phenylalanine (AA-Ext). These data show an acute increase in parenteral amino acid–suppressed proteolysis, however, such an effect was not seen when amino acids were infused for 20 h and resulted in an increase in glutamine synthesis.