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Biomedical subjects

D M Bier

Publications and source records attributed to D M Bier.

At least 145 records · Page 8Linked to original sources
PubMed1981

Regulation of leucine metabolism in man: a stable isotope study.

Leucine catabolism is regulated by either of the first two degradative steps: (reversible) transamination to the keto acid or subsequent decarboxylation. A method is described to measure rates of leucine transamination, reamination, and keto acid oxidation. The method is applied directly to humans by infusing the nonradioactive tracer, L-[15N,1-13C]leucine. Leucine transamination was found to be operating several times faster than the keto acid decarboxylation and to be of equal magnitude in adult human males under two different dietary conditions, postabsorptive and fed. These results indicate that decarboxylation, not transamination, is the rate-limiting step in normal human leucine metabolism.

Adult↗
PubMed1981

Direct measurement of gluconeogenesis from [2,3]13C2]alanine in the human neonate.

The functional integrity of the gluconeogenic pathway was measured in nine term infants, four appropriate-for-gestational age (AGA), and five normoglycemic small-for-gestational age (SGA), by determination of 13C2 enrichment in blood glucose during the constant infusion of tracer [2,3]13C2]alanine between 4 and 8 h of postnatal age. Alanine flux, calculated from the steady-state blood [2,3-13C2]alanine enrichment was 16.6 +/- 1.3 (SE) (mumol.kg-1.min-1 in the AGA infants and not statistically different from the value of 15.3 +/- 0.7 mumol.kg-1.min-1 in the SGA infants. Alanine flux did not correlate with blood alanine level in either group. By 6 h of age, the earliest sampling time, there was 13C2 enrichment of blood glucose in every infant studied, indicating that the gluconeogenic pathway was functionally intact by that time and implying that it was operative sooner. At 8 h of age, 9.3 +/- 2.3% of blood glucose was derived from alanine in the AGA group and 12.9 +/- 2.4% in the SGA group, values not statistically different. These data indicate that the term human newborn has a functional gluconeogenic pathway very early in postnatal life and that intrauterine growth retardation per se does not impair maturation of the system. Furthermore, the plasma alanine level alone is a poor index of gluconeogenic carbon flow in these infants.

Adult↗
PubMed1981

Whole-body leucine and lysine metabolism: response to dietary protein intake in young men.

Whole-body leucine and lysine metabolism was explored in young adult men by a primed constant intravenous infusion of a mixture of L-[1-13C]leucine and L-[alpha-15N]lysine over a 4-h period. Subjects were studied after an overnight fast (postabsorptive state) or while consuming hourly meals (fed state) after adaptation to diets providing either a surfeit level of protein (1.5 g.kg body-1.day-1), a level approximating maintenance requirements (marginal intake) (0.6 g.kg body wt-1.day-1), or a grossly inadequate level (0.1 g.kg-1.day-1). The change in protein intake from a marginal to a surfeit level was associated with an increased leucine flux and incorporation of leucine into body protein. In the fed state, oxidation of leucine increased sharply and release of leucine from tissue protein diminished. When dietary protein intake was reduced from the requirement to inadequate level, leucine flux and body protein synthesis and protein breakdown were reduced, together with a smaller reduction in leucine oxidation. The response of the metabolism of [15N]lysine was responsible for maintenance of leucine and other essential amino acid economy, and they appear to be related to the nitrogen and amino acid requirements of the subject. These findings also demonstrate an effect of meals, modulated by their protein content, on the dynamics of whole-body amino acid metabolism.

Adolescent↗
PubMed1981

Epinephrine plasma thresholds for lipolytic effects in man: measurements of fatty acid transport with [l-13C]palmitic acid.

To determine the plasma epinephrine thresholds for its lipolytic effect, 60-min epinephrine infusions at nominal rates of 0.1, 0.5, 1.0, 2.5, and 5.0 micrograms/min were performed in each of four normal young adult men while they also received a simultaneous infusion of [1-13C]palmitic acid to estimate inflow transport of plasma free fatty acids. These 20 infusions resulted in steady-state plasma epinephrine concentrations ranging from 12 to 870 pg/ml. Plasma epinephrine thresholds for changes in blood glucose, lactate, and beta-hydroxybutyrate were in the 150--200-pg/ml range reported by us previously (Clutter, W. E., D. M. Bier, S. D. Shah, and P. E. Cryer. 1980. J. Clin. Invest. 66: 94--101.). Increments in plasma glycerol and free fatty acids and in the inflow and outflow transport of palmitate, however, occurred at lower plasma epinephrine thresholds in the range of 75 to 125 pg/ml. Palmitate clearance was unaffected at any steady-state epinephrine level produced. These data indicate that (a) the lipolytic effects of epinephrine occur at plasma levels approximately threefold basal values and (b) lipolysis is more sensitive than glycogenolysis to increments in plasma epinephrine.

Adult↗
PubMed1980

An improved selected ion recording system for precise isotope ratio determination.

An improved analog four-channel selected ion recording system is described, in which major modifications permit a decrease in the dwell time to 33 ms per channel, thus minimizing the mass cycling error. Synchronization with a sinusoidal sweep voltage superimposed on the normal accelerating voltage (8 kV) enables two channels to be monitored simultaneously in real time and each mass to be recorded continuously. These improvements allow measurement of ion current ratios with a precision of 0.2% over a wide dynamic range, permitting accurate determination of isotopic enrichment in biomedical assays even when this enrichment is derived from a single label. Use of the system is illustrated by the analysis of palmitate turnover in dogs (using [1--13C] palmitic acid) with an average standard deviation corresponding to the detection of 0.04% excess of [1--13C] palmitate.

Animals↗
PubMed1980

Effects of dietary intake and hemodialysis on protein turnover in uremic children.

The dynamic aspects of protein metabolism in uremic children were studied by using newly developed gas chromatography and mass spectrometry micromethods for determining nitrogen-15 enrichment in plasma lysine during a continuous i.v. infusion of 15N-lysine. Protein flux in uremic children was low and varied directly with protein and energy intake, which themselves were closely related in the diets consumed by the study subjects. Hemodialysis did not alter acutely protein flux. Protein flux in children undergoing chronic hemodialysis was still reduced below normal but was higher than that in nondialyzed uremic children at each level of protein-energy intake. The ratio of protein flux to protein intake was 0.05 +/- 0.003 g of protein x kg-1 x day-1 x kcal ingested in the nondialyzed uremic children, but it increased to a normal vaue of 0.11 +/- 0.03 g x kg-1 x day-1 x kcal in those on longterm hemodialysis. We conclude that the low protein turnover rates in our uremic population reflect the decreased protein-energy intake commonly found in such patients and that reduction of azotemia by chronic hemodialysis may improve whole body transport at a given energy intake.

Adolescent↗
PubMed1980

Measurement of leucine metabolism in man from a primed, continuous infusion of L-[1-3C]leucine.

Leucine metabolism in vivo can be determined from a primed, continuous infusion of L-[1-13C]leucine by measuring, at isotopic steady state, plasm [-13C]leucine enrichment, expired 13CO2 enrichment, and CO2 production rate. With an appropriate priming dose of L-[1-13C]leucine and NaH13CO3, isotopic steady state is reached in less than 2 h, and the infusion is completed in 4 h. The method can determine rates of leucine turnover, oxidation, and incorporation into protein with typical relative uncertainties of 2, 10, and 4%, respectively. The method requires no more than 1 ml of blood and uses stable isotope rather than radioisotope techniques. Thus, the method is applicable to studies of human beings of all ages. L-[1-13C]leucine may be infused with a second amino acid labeled with 15N for simultaneous determination of the kinetics of two amino acids.

Adolescent↗
PubMed1980

Epinephrine plasma metabolic clearance rates and physiologic thresholds for metabolic and hemodynamic actions in man.

To determine the plasma epinephrine thresholds for its metabolic and hemodynamic actions and plasma epinephrine metabolic clearance rates, 60-min intravenous epinephrine infusions at nominal rates of 0.1, 0.5, 1.0, 2.5, and 5.0 microgram/min were performed in each of six normal human subjects. These 30 infusions resulted in steady-state plasma epinephrine concentrations ranging from 24 to 1,020 pg/ml. Plasma epinephrine thresholds were 50-100 pg/ml for increments in heart rate, 75-125 pg/ml for increments in blood glycerol and systolic blood pressure, 150-200 pg/ml for increments in plasma glucose (the resultant of increments in glucose production and decrements in glucose clearance), blood lactate, blood beta-hydroxybutyrate, and diastolic blood pressure, and greater than 400 pg/ml for early decrements in plasma insulin. Changes in blood alanine, plasma glucagon, plasma growth hormone, and plasma cortisol were not detected. At steady-state plasma epinephrine concentrations of 24-74 pg/ml, values overlapping the basal normal range, the mean (+/-SE) plasma metabolic clearance rate of epinephrine was 52 +/- 4 ml x min-1 x kg-1; this value rose to 89 +/- 6 ml x min-1 x kg-1 (P less than 0.01) at steady-state epinephrine concentrations of 90-1,020 pg/ml. We conclude that in human subjects: (a) the plasma epinephrine thresholds for its hemodynamic and metabolic actions lie within the physiologic range, (b) epinephrine and norepinephrine accelerate their own metabolic clearance, and (c) epinephrine is 10 times more potent than norepinephrine.

Adult↗
PubMed1980

Branched-chain amino acid nitrogen transfer to alamine in vivo in dogs. Direct isotopic determination with [15N]leucine.

To investigate the contribution of branched-chain amino acids as a nitrogen source for alanine in vivo, dogs were infused with l-[(15)N]leucine, l-[U-(14)C]leucine, l-[2,3,3,3-(2)H(4)]alanine, and d-[6,6-(2)H(2)]-glucose. (14)C and (15)N isotopic equilibrium in plasma leucine, and deuterium enrichment in arterial and femoral plasma glucose and alanine were achieved within 3 h of initiation of the respective isotope infusion in all animals. The average flux of leucine determined by [(15)N]leucine was 5.4 mumol.kg(-1).min(-1), whereas using [(14)C]leucine it was 3.7 mumol.kg(-1).min(-1). Turnover rates for alanine and glucose were 11.0 and 17.2 mumol.kg(-1).min(-1), respectively.[(15)N]alanine was detected as early as 30 min, but nitrogen isotopic equilibrium in alanine was not achieved until 6 h. The absolute rate of leucine nitrogen transfer to alanine was 1.92 mumol.kg(-1).min(-1), which represented 41-73% (mean 53%) of leucine's nitrogen and 15-20% (mean 18%) of alanine's nitrogen. Fractional extraction of alanine and leucine by the dog hindlimb was 35 and 24%, respectively. Average net alanine balance was -6.7 mumol.leg(-1).min(-1), reflecting a release rate (17.4 mumol.kg(-1).min(-1)) that exceeded the rate of uptake (10.8 mumol.leg(-1).min(-1)). Of the leucine taken up by the hindlimb, 34% transferred its nitrogen to alanine and 8% was oxidized to CO(2). Since the latter value reflects transamination as well as irreversible catabolism, the nitrogen derived from the oxidation of leucine by the hindlimb could account for only 25% of the observed (15)N incorporation into alanine. The significantly faster flux of leucine nitrogen when compared with leucine carbon suggests significant recycling of the leucine alpha-ketoacid. These studies demonstrate that leucine is a major donor of nitrogen to circulating alanine in vivo.

Alanine↗
PubMed1980

Alloisoleucine formation in maple syrup urine disease: isotopic evidence for the mechanism.

Of the four possible stereoisomers of isoleucine, only L-alloisoleucine and L-isoleucine were found by capillary gas chromatography in the plasma of two maple syrup urine disease (MSUD) patients, one with classical and one with variant MSUD. The relative plasma concentration ratios of L-alloisoleucine/L-isoleucine were 0.795 +/- 0.025 (+/- 95% confidence limits) and 0.637 +/- 0.016 in the classical- and variant-MSUD patients, respectively. The patients were also studied in the postabsorptive state with a 6-hr continuous infusion of L-[15N]leucine. In each patient plasma leucine 15N enrichment approximated plateau after 150 min, and there was rapid appearance of [15N]isoleucine and [15N]alloisoleucine which were identical at plateau, although in variant-MSUD patient [15N]alloisoleucine enrichment did not equal that of [15N]isoleucine until 240 min of infusion. These results offer direct in vivo evidence for the rapid equilibrium of plasma isoleucine and alloisoleucine through keto-enol tautomerization of alpha-keto-beta-methylvalerate.

Child↗
PubMed1980

Glucose perturbation in experimental hyperviscosity.

Hyperviscosity was produced in one member of each of 7 sets of twin newborn lambs by an exchange transfusion with 500 ml maternal packed red blood cells. The remaining seven control twin lambs underwent an identical exchange with maternal whole blood. Postexchange hematocrits were 63 +/- 6 and 29.0 +/- 3% (mean +/- S.E.), respectively (P less than 0.01). Whole blood viscosity measured at 3 rpm increased from 3.2 +/- 0.4 centipoise (cps) to 14.4 +/- 6.1 cps in the lambs made hyperviscous (P less than 0.01) and remained unchanged in the control lambs (2.2 +/- 0.1 versus 2.8 +/- 0.3 cps). A 2-hr steady state glucose infusion was performed on each lamb before and after the packed cell or whole blood exchange transfusion. Mean steady state plasma glucose concentrations were significantly decreased from pre-exchange steady state glucose infusion levels in the same lambs made hyperviscous (P less than 0.05), whereas steady state glucose levels increased from preexchange levels in the twin lambs exchanges with maternal whole blood. Mean plasma insulin and glucagon values for the hyperviscous and control lambs remained unchanged during the glucose infusion.

Animals↗
PubMed1980

Estimation of glucose turnover and 13C recycling in the human newborn by simultaneous [1-13C]glucose and [6,6-1H2]glucose tracers.

To compare two methods of estimating systemic glucose production rates and to quantify carbon tracer recycling, six newborn infants, aged 2 h to 3 days, were infused simultaneously with [1-13C]glucose and [6,6-2H2]glucose tracers. The older infants were studied 6 h after a meal. [1-13C]Glucose was infused at 6 microgram/kg.min. Systemic glucose production rates were calculated from tracer dilution, assuming steady state kinetics. Although 13C was expected to randomize away from the C-1 of glucose, recycling occurred and was estimated from the difference in the rate of systemic glucose production quantified by the dilution of the two tracers. Systemic glucose production rates ranged from 4.2--5.4 mg/kg.min. Recycling on the glucose C-1 was 3--20% of the systemic glucose production rate and did not change with the age of the infant. Because recycling of glucose carbon signifies gluconeogenesis from lactate or pyruvate, it is concluded that the human newborn is able to initiate gluconeogenesis soon after birth.

Blood Glucose↗