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Biomedical subjects

D M Bier

Publications and source records attributed to D M Bier.

At least 91 records · Page 5Linked to original sources
PubMed1988

Glucose and amino acid metabolism in aging man: differential effects of insulin.

Insulin is a major regulator of glucose and body protein homeostasis, both of which demonstrate age-related changes. To clarify insulin's role in these age-related changes and to compare age-related glucose and protein homeostatic responses, insulin-mediated aspects of glucose and amino acid metabolism were simultaneously examined in healthy postabsorptive young (n = 5, mean age, 25 years) and elderly (n = 5, mean age, 76 years) men. Primed constant infusions of L-[1-13C]leucine and L-[15N]alanine were administered during a basal period (0 to 180 minutes) and during four separate single rate euglycemic insulin infusions (180 to 360 minutes). Steady state insulin concentrations were 16 +/- 1, 29 +/- 3, 75 +/- 5, and 2407 +/- 56 microU/mL in the young and 23 +/- 4, 37 +/- 8, 96 +/- 11 and 3,357 +/- 249 microU/mL in the elderly at the different insulin infusion rates of 6, 10, 30, and 400 mU mU.m-2.min-1, respectively. For the 6 and 10 mU insulin infusion rates, a primed, constant infusion of [6,6 - 2H2]glucose permitted quantitation of hepatic glucose production. Glucose disposal rates adjusted for lean body mass (LBM) were lower in the elderly than in the young at the 6, 10, and 30 mU insulin infusion rates and similar in the two age groups in the 400 mU studies. Insulin dose-dependent reductions occurred in eight of ten plasma amino acids and were not influenced by age. There was an insulin dose-dependent reduction in plasma leucine flux which was similar in both age groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Alanine flux in obese and healthy humans as evaluated by 15N- and 2H3-labeled alanines.

Estimates of plasma alanine flux as measured in humans using L-[15N]-alanine or L-[3,3,3-2H3]alanine were compared by simultaneous intravenous infusion of both tracers. Plasma isotope enrichments were measured by chemical ionization gas chromatography-mass spectrometry. In 16 obese women before and during a hypocaloric diet and in 4 normal men in the postabsorptive and fed states, the fluxes were highly correlated (r2 = 0.93) although plasma alanine flux with the 2H tracer was two to three times greater than that obtained with [15N]alanine. The fluxes decreased with the hypocaloric diet in obese subjects and increased during the fed state in healthy adults. Thus, although the estimates of alanine flux differed according to the tracer used, both appear to give equivalent information about changes in alanine kinetics induced by the nutritional conditions examined.

Adult↗
PubMed1988

Leucine kinetics at graded intakes in young men: quantitative fate of dietary leucine.

To explore leucine metabolism in relation to leucine intake, five young adult men received an L-amino acid diet that supplied 40, 30, 20, and 10 mg leucine.kg-1.d-1 for 6 d. A stable-isotope-tracer infusion study was then conducted for 5 h while subjects received an intragastric infusion of the test diet. Primed, constant infusions of L-[1-13C]leucine (intragastric) and L-[2H3]leucine (intravenous) were given simultaneously. A final infusion study was conducted in subjects in the postabsorptive state after an additional 2 d with the 10-mg diet. Estimates were made of leucine flux and oxidation, rates of uptake and release of absorbed leucine by the splanchnic region, and leucine balance. The rate of appearance of dietary leucine in the systemic circulation (Leud) decreased (p less than 0.01) between the 40- and 10-mg diets. At the latter intake, splanchnic uptake was approximately 37% of absorbed leucine. The correlation between Leud and plasma leucine concentration was highly positive. A leucine intake of approximately 40 mg. kg-1.d-1 was close to that required to maintain leucine balance under these conditions.

Adult↗
PubMed1988

Physiological hypercortisolemia increases proteolysis, glutamine, and alanine production.

Physiological elevations of plasma cortisol levels, as are encountered in stress and severe trauma, were produced in six normal subjects by infusing them with 140 micrograms.kg-1.h-1 of hydrocortisone for 64 h. Amino acid kinetics were measured in the postabsorptive state using three 4-h infusions of L-[1-13C]leucine, L-[phenyl-2H5]-phenylalanine, L-[2-15N]glutamine, and L-[1-13C]alanine tracers 1) before, 2) at 12 h, and 3) at 60 h of cortisol infusion. Before and throughout the study, the subjects ate a normal diet of adequate protein (0.8 g.kg-1.day-1) and energy intake. The cortisol infusion raised plasma cortisol levels significantly from 10 +/- 1 to 32 +/- 4 micrograms/dl, leucine flux from 83 +/- 3 to 97 +/- 3 mumol.kg-1.h-1, and phenylalanine flux from 34 +/- 1 to 39 +/- 1 (SE) mumol.kg-1.h-1 after 12 h of cortisol infusion. These increases were maintained until the cortisol infusion was terminated (64 h). These nearly identical 15% increases in two different essential amino acid appearance rates are reflective of increased whole body protein breakdown. Glutamine flux rose from 325 +/- 28 to 453 +/- 28 mumol.kg-1.h-1 by 12 h of cortisol infusion and remained elevated at the same level at 64 h. The increase in flux was primarily due to a 55% increase in glutamine de novo synthesis. Alanine flux increased from 207 +/- 13 to 285 +/- 23 mumol.kg-1.h-1 with acute hypercortisolemia and increased further to 475 +/- 59 mumol.kg-1.h-1 at 60 h of cortisol infusion, a result primarily of increased alanine de novo synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Regulation of adult and fetal myocardial phosphofructokinase. Relief of cooperativity and competition between fructose 2,6-bisphosphate, ATP, and citrate.

To clarify the physiological role of fructose 2,6-bisphosphate in the perinatal switching of myocardial fuels from carbohydrate to fatty acids, the kinetic effects of fructose 2,6-bisphosphate on phosphofructokinase purified from fetal and adult rat hearts were compared. For both enzymes at physiological pH and ATP concentrations, 1 microM fructose 2,6-bisphosphate induced a greater than 10-fold reduction in S0.5 for fructose 6-phosphate and it completely eliminated subunit cooperativity. Fructose 2,6-bisphosphate may thereby reduce the influence of changes in fructose 6-phosphate concentration on phosphofructokinase activity. Based on double-reciprocal plots and ATP inhibition studies, adult heart phosphofructokinase activity is more sensitive to physiological changes in ATP and citrate concentrations than to changes in fructose 2,6-bisphosphate concentrations. Fetal heart phosphofructokinase is less sensitive to ATP concentration above 5 mM and equally sensitive to citrate inhibition. The fetal enzyme has up to a 15-fold lower affinity for fructose 2,6-bisphosphate, rendering it more sensitive to changes in fructose 2,6-bisphosphate concentration than adult heart phosphofructokinase. Together, these factors allow greater phosphofructokinase activity in fetal heart while retaining sensitive metabolic control. In both fetal and adult heart, fructose 2,6-bisphosphate is primarily permissive: it abolishes subunit cooperativity and in its presence phosphofructokinase activity is extraordinarily sensitive to both the energy balance of the cell as reflected in ATP concentration and the availability of other fuels as reflected in cytosolic citrate concentration.

Adenosine Triphosphate↗
PubMed1987

Bioavailability of dietary urea nitrogen in the infant.

Because the human body has no enzymes capable of hydrolyzing urea, nitrogen from this source becomes bioavailable only by release of ammonia from urea by bacterial hydrolysis in the intestines, with subsequent absorption and utilization of ammonia. To explore extent to which urea ingested in milk becomes bioavailable, we fed di-15N-urea (both nitrogen atoms in the form of the stable isotope 15N) and determined urinary excretion of di-15N-urea (excreted without having become bioavailable) and mono-15N-urea (urea containing only one atom of 15N and therefore reflecting excretion of absorbed ammonia). The largest percentage of the ingested di-15N-urea was excreted promptly in the urine still in the form of di-15N-urea. We conclude that most of the urea ingested by a normal infant is not bioavailable.

Animals↗
PubMed1987

The use of stable isotopes in metabolic investigation.

The use of tracers to define substrate dynamics has been the sine qua non of metabolic investigation in vivo, because static measurements of substrate content alone are inadequate. The judicious use of radioactively labelled compounds remains the principal tracer approach in some adult subjects. However, in certain young adults, in pregnant women and in children, stable isotope tracers offer a practical alternative for answering important metabolic questions. In the last decade, the developmental problems previously associated with employing stable isotope tracers for this purpose have largely disappeared. Furthermore, the use of stable isotopically labelled materials offers certain additional advantages which are either difficult or impossible to achieve using radiotracers. These include the ability to measure simultaneously substrate content and isotopic enrichment with very high specificity and precision, the ability to determine the intramolecular location of the label, the ability to use the mass of the stable isotope substrate as a probe of the metabolite system response to perturbation, and the ability to study simultaneously and repeatedly the same subject with multiple substrate tracers. The practical application of these principles has been amply demonstrated by the expanding use of non-radioactive tracers to study body composition, energy balance, and the inter-organ transport and oxidation of the three major metabolic fuels--glucose, fat and amino acids. Continued development in the organic synthesis of new, stable isotopically labelled biochemicals will allow investigation of additional areas of biomedical importance which have been hitherto inaccessible to this approach, particularly in the pathophysiology of metabolic events in the growing child.

Body Composition↗
PubMed1987

Physiological increments in epinephrine stimulate metabolic rate in humans.

Markedly elevated plasma epinephrine is known to increase metabolic rate (MR), but such levels of epinephrine are encountered infrequently in normal free-living subjects. We studied whether epinephrine levels common in usual daily activities can affect MR and thus possibly regulate caloric expenditure. To aid definition of a MR threshold, we first measured the hourly and daily variation in MR within individuals by measuring the MR of four individuals by indirect calorimetry for 6 h on six separate occasions without any intervention. We found that hour-to-hour variation (2.0 +/- 0.9%) and the day-to-day variation (2.7 +/- 0.9%) were low, thus allowing confident detection of small increments in metabolic rate during epinephrine infusion. To define a threshold for epinephrine's effect to increase MR, we studied five normal-weight postabsorptive young men on four separate occasions. During the 1st h of each 5-h study period, saline was infused intravenously. Then, during the subsequent 4 h, subjects received intravenous infusion of saline or epinephrine at 0.1, 0.5, and 1.0 microgram/min (randomized). A significant increase in MR (3.6 +/- 1.0% SE) was measured with the lowest epinephrine infusion rate (venous plasma concentration, 94 +/- 32 pg/ml). The increases in MR correlated (r = 0.85, P less than 0.001) with increases in plasma epinephrine. The threshold concentration (upper 95% confidence limit) of epinephrine to affect MR was 90 pg/ml, a concentration frequently occurring in daily life. Thus epinephrine may play an important role in weight maintenance by affecting energy expenditure.

Adult↗
PubMed1987

Models to interpret kinetic data in stable isotope tracer studies.

In contrast to "weightless" radioactive tracers, stable isotope tracers have nonnegligible mass and are naturally present in the system, and the measured variable is a ratio of two isotopic species. These features do not allow stable isotopic tracer data analysis using straightforward analogy with radioactive tracer approaches, even though this practice is common. In this study, we present kinetic variables, models, and measurements for the analysis and interpretation of stable isotope tracer data. Assumptions and mathematical techniques for modeling the data when perturbation is both nonnegligible and negligible are discussed. Emphasis is placed on the rich information content of the dynamic portion of a stable isotope tracer curve and on the role of compartmental and noncompartmental modeling approaches for its interpretation. A presumed and commonly used analogy between the radioactive specific activity and stable isotopic enrichment is shown to be incorrect. We show that the proper analogue of specific activity is the tracer-to-tracee molar ratio. This variable is not a directly measurable one, but a formula is derived that allows its computation from the data. A method for reconstructing the time course in blood of the concentration component due to endogenous synthesis is presented. This allows measurement of the extent of the perturbation in the case where a nonweightless tracer is used. Special attention is given to data analysis originating from a multiple tracer experiment, a configuration necessary for studying more complex systems, e.g., the kinetics of interacting substrates.

3-Hydroxybutyric Acid↗
PubMed1987

Leucine kinetics during three weeks at submaintenance-to-maintenance intakes of leucine in men: adaptation and accommodation.

Previous results of short-term diet studies of leucine kinetics have suggested that the currently accepted requirement value for the amino acid in adults is too low. In the present study the effects of a more prolonged diet period at low leucine intakes on leucine kinetics and nitrogen balance (NB) were explored in healthy young men. They (4 or 5 subjects per group) received an adequate leucine intake (80 mg/kg/d) for 1 or 2 weeks (Period 1) followed by either 7, 14 or 30 mg/kg/d for 3 weeks (Period 2) with a return to 80 mg/kg/d for 1 week (Period 3). Estimates of leucine fluxes (LF), oxidation (LO) and balance (LB) were based on a constant intravenous infusion of L-[1-13C]leucine, at end of Period 1, at 1 and 3 weeks of Period 2 and on days 1 and 3 of Period 3. At all three intakes LF and LO, during the fed state, fell between 1 and 3 weeks of Period 2. LB was negative at 1 week of Period 2 for all groups but had approached equilibrium by 3 weeks. N balance at 3 weeks was similar for all groups but during Period 3 was significantly higher (P less than 0.05) and markedly positive (+18 mgN/kg/d) for the 7 and 14 mg groups, compared with the 30 mg group (+4 mgN/kg/d), indicating that 'depletion' had occurred at the lower leucine intakes during Period 2. Our interpretation is that LB was approached by an adaptation in the 30 mg group whereas it was achieved in the 7 and 14 mg groups by an accommodation, associated with a reduced and low rate of leucine uptake into protein (LF minus LO). Thus, the leucine requirement was judged to be greater than 14 mg/kg/d, a level currently accepted as the upper range of the requirement for healthy adults. The significance of these findings for assessment of nutrient requirements is discussed, with emphasis on the limitation of NB measurements for evaluation of human amino acid requirements.

Adaptation, Biological↗
PubMed1986

Leucine kinetics at graded leucine intakes in young men.

A study was carried out with 12 young men to examine the relationships between the intake of leucine and indices of leucine kinetics, using L-[1-13C]leucine as a tracer. Six subjects received L-amino acid diets during 7-day periods supplying leucine in the range of 79 to 20 mg.kg-1.day-1 (Group I) and another six subjects (Group II) received leucine intakes ranging from 20 to 4 mg.kg-1.day-1. Estimations were made of leucine kinetics, at the end of each diet period, when subjects were receiving small isonitrogenous, isocaloric meals during the isotope infusion period. Leucine flux declined with reduced leucine intake and leucine oxidation tended not to change at intakes below 20 mg.kg-1.day-1 (slope not statistically different than zero). Plasma valine increased markedly with further restriction in leucine intake below this level. The daily mass balance of leucine, estimated from the difference between intake and oxidation, became negative at an intake of about 20 mg.kg-1.day-1. These findings are discussed in relation to the published mean and upper range of requirement for leucine in healthy adults, currently taken to be 11 mg.kg-1.day-1 and 14 mg.kg-1.day-1, respectively.

Adolescent↗
PubMed1986

Valine kinetics at graded valine intakes in young men.

Twelve young men, six subjects in each group studied in two phases, participated in an experiment to explore the relationships between valine intake, plasma valine concentrations, and valine kinetics, using 1-[13C]valine as a tracer. Below a valine intake of about 20 mg.kg-1.day-1 plasma valine concentrations reached a low and relatively constant level. The rate of valine oxidation fell with the decline in the intake of amino acid. Below valine intakes of 16 mg.kg-1.day-1, the mean daily rate of oxidation was estimated to be generally higher than the intake level, implying a negative valine balance during the 24 h day. These findings indicate that an intake of 10 mg valine kg-1.day-1 would not be adequate to maintain protein nutritional status. Our results are discussed in relation to the currently accepted 1973 FAO/WHO value of 10 mg.kg-1.day-1 as being the upper range of the valine requirement in healthy adult humans.

Adolescent↗
PubMed1986

Lysine kinetics at graded lysine intakes in young men.

Healthy young men participated in a study designed to explore the effects of decreasing dietary lysine content on plasma amino acid concentrations and lysine kinetics, studied with L-[1-13C]lysine as tracer. Diets provided adequate energy and the equivalent (N X 6.25) of 0.8 g protein kg-1.day-1 as a synthetic L-amino acid mixture simulating egg protein. Lysine intake was reduced every 7 days. Changes in plasma amino acids suggested that effects characteristic of a dietary lysine inadequacy were prevented by consuming more than 32 mg lysine.kg-1 day-1. Primed, continuous intravenous infusions of L-[1-13C]lysine, at the end of each diet period while subjects were in the fed state, showed that as dietary lysine was reduced, 13C enrichment increased in plasma lysine and decreased in expired CO2. It was estimated that lysine oxidation exceeded, by 4.4 mg kg-1 day-1, the lysine intake of 20 mg kg-1.day-1 indicating that the lysine required for body protein maintenance would probably exceed this latter value. These results are discussed in relation to the physiological requirement in adults for lysine, currently accepted to be met by an intake of 12 mg kg-1.day-1. which is assumed to be the upper range of the lysine requirement for this population group.

Adolescent↗
PubMed1986

Threonine kinetics at graded threonine intakes in young men.

A study was undertaken in eight healthy young men to examine the effects of varying intakes of threonine on plasma free threonine concentrations and threonine kinetics, using a 3 h constant intravenous infusion of L-[1-13C]threonine. Subjects consumed diets based on an L-amino acid mixture, in which the quality of threonine was reduced every 7 days. On the last day of each diet period, determinations of plasma threonine flux and threonine oxidation were carried out while subjects consumed small meals, each supplying 1/12 daily intake, at hourly intervals. Threonine oxidation rates fell with reduced threonine intake, reaching a relatively constant level at intakes of 20 mg.kg-1.day-1 and below. These metabolic data are discussed in relation to the currently established value of 7 mg.kg-1.day-1 as the upper range of the threonine requirement for healthy young adults. It is concluded that actual threonine requirements may be considerably higher for this age group.

Adolescent↗