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Biomedical subjects

D E Matthews

Publications and source records attributed to D E Matthews.

At least 109 records · Page 6Linked to original sources
PubMed1989

Stimulation of protein turnover by carbohydrate overfeeding in men.

The effect of carbohydrate overfeeding on protein metabolism was studied in 11 healthy men. Total urinary nitrogen output during 10 days of carbohydrate overfeeding (1,600 extra kcal/day) decreased 27% relative to nitrogen excretion during 10 days of weight maintenance, indicating protein accretion during over-feeding. However, postabsorptive nitrogen excretion did not change, which means that the positive nitrogen balance associated with overfeeding results from enhanced postprandial nitrogen retention. Overfeeding reduced postabsorptive glucose concentrations 4 +/- 1% and increased glucose production rate 14 +/- 2% and glucose clearance 17 +/- 4%. Overfeeding increased plasma concentrations of insulin, glucagon, and 3,5,3'-triiodothyronine approximately 20%. Alanine and branched-chain amino acid concentrations were increased after overfeeding, but serine, threonine, and asparagine concentrations were reduced. Postabsorptive leucine flux, which is an index of proteolysis, was measured using L-[1-13C]leucine as a tracer. Overfeeding increased leucine flux 13 +/- 2% compared with values after 10 days on a weight-maintenance diet. If it is assumed that overfeeding did not alter the fraction of 13CO2 not recovered in breath, there was no change in the portion of leucine flux that was oxidized. Thus the difference between flux and oxidation, which is a theoretical index of protein synthesis, increased 12 +/- 3% after overfeeding. These data suggest that excess caloric intake, without an increase in protein intake, stimulates post-absorptive proteolysis and protein synthesis.

Adult↗
PubMed1988

Glutamine and glutamate nitrogen exchangeable pools in cultured fibroblasts: a stable isotope study.

Glutamine's role as an energetic fuel has been extensively studied in the past using 14C- and 3H-labeled tracers in cultured human cells. Yet another prominent role of glutamine, that of a nitrogen shuttle, cannot be approached without an N-tracer. We therefore used 15N-labeled glutamine and glutamate to address the following questions: 1) is it possible to study the exchangeable pools of intracellular free glutamine and glutamate nitrogen with stable isotope methods? and 2) to what extent is intracellular glutamine pool regulated by extracellular glutamine? We observed that: 1) intracellular [15N]-glutamine enrichment reached a plateau at 80% within 20 min of incubation in a buffer containing 0.7 mM pure 15N-glutamine and no glutamate; in contrast, intracellular 15N-glutamate enrichment rose only to 40% after 4 hours of incubation in a buffer containing 0.5 mM pure 15N-glutamate and no glutamine; 2) the cell-free glutamine content was tightly dependent on extracellular glutamine level, while the cell-free glutamate remained steady irrespective of the extracellular glutamate level; 3) the cells took up glutamine and glutamate against a concentration gradient; the rate of glutamine uptake accounted for 90% of the cell glutamine turnover rate; and 4) when cells were confronted with a glutamine-free medium, only one fourth of intracellular glutamine was derived from the exchangeable glutamate. We conclude that: 1) The size and turnover rate of the intracellular pool of free glutamine nitrogen are measureable using stable isotope methodology; 2) glutamine uptake from the extracellular medium accounts for most of glutamine turnover rate in cultured fibroblasts; and 3) intracellular free glutamate is divided up between several pools in cultured human fibroblasts.

Body Fluids↗
PubMed1988

The effect of increased intracranial pressure (ICP) on gastric motility.

This study evaluates the effect of increased intracranial pressure (ICP) on gastric motility. Nine male cats (weight, 4.84 +/- 1.16 kg) were anesthetized with ketamine and underwent laparotomy for placement of bipolar (silver-silver chloride) electrodes on the serosal surface of the gastroesophageal junction (GEJ), antrum, and prepyloric areas of the stomach. At 1 week frontoparietal burr holes were performed with placement of an epidural Fogarty catheter. Migrating myoelectric complexes (MMCs) were evaluated at the GEJ, antrum, and prepyloric areas at varying levels of ICP (baseline and 20, 40, and 60 mm Hg) using balloon inflation. MMCs at the GEJ were triphasic with a period of 4 sec (+/- 1 sec) at baseline levels. At ICP levels above baseline, periodicity and waveforms at the GEJ became irregular. Waveforms became multiphasic with 1- to 2-sec periods and variable amplitudes. In the antral and prepyloric areas, duration and amplitude of the triphasic MMCs was unchanged from baseline. At 60 mm Hg ICP periodicity was significantly altered at both 1 and 2 weeks. MMCs returned to baseline levels with balloon deflation. The data indicate that elevated ICP (to 60 mm Hg) results in consistent and reproducible alterations of MMC periodicity, suggesting that such alterations may influence gastric motility.

Animals↗
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

Protein and substrate metabolism during starvation and parenteral refeeding.

1. Healthy male volunteers underwent 10 days of hospitalized protein-calorie starvation and a subsequent 10 day repletion phase with complete intravenous nutritional support (IVF). Non-protein calories were provided as either all D-glucose or as 50% D-glucose/50% lipid. 2. In comparison with starvation, whole-body protein breakdown, as assessed by [15N]glycine, [13C]leucine and urinary excretion of 3-methylhistidine (3-MH), was diminished during IVF. The administration of parenteral nutrition did not specifically suppress peripheral tissue protein breakdown, as measured by extremity 3-MH efflux. 3. Despite the differential insulin response to D-glucose/amino acid (50 +/- 6 m-units/ml) as compared with the D-glucose/lipid/amino acid regimen (25 +/- 4 m-units/ml), there was no difference in nitrogen retention between the regimens. Indirect calorimetric determinations revealed that oxidation of substrate during IVF was related to the proportion of D-glucose and lipid infusion.

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

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

Leucine, glucose, and energy metabolism after 3 days of fasting in healthy human subjects.

Adaptations of leucine and glucose metabolism to 3 d of fasting were examined in six healthy young men by use of L-[1-13C]leucine and D[6,6-2H2]glucose as tracers. Leucine flux increased 31% and leucine oxidation increased 46% after 3 d of fasting compared with leucine flux and oxidation after an overnight fast. Glucose production rate declined 38% and resting metabolic rate decreased 8% during fasting. Plasma concentrations of testosterone, insulin, and triiodothyronine were reduced by fasting whereas plasma glucagon concentrations were increased. We conclude that there is increased proteolysis and oxidation of leucine on short-term fasting even though glucose production and energy expenditure decreased.

Adult↗
PubMed1987

Role of oxygenases in pisatin biosynthesis and in the fungal degradation of maackiain.

Some isolates of the plant pathogen Nectria haematococca detoxify the isoflavonoid phytoalexin (-)maackiain by hydroxylation at carbon 6a. Precursor feeding studies strongly suggest that the penultimate step in (+)pisatin biosynthesis by Pisum sativum is 6a-hydroxylation of (+)maackiain. We have used (18)O labeling to test the involvement of oxygenases in these two reactions. When fungal metabolism of maackiain took place under (18)O(2), the product was labeled with 99% efficiency; no label was incorporated by metabolism in H(2) (18)O. Pisatin synthesized by pea pods in the presence of (18)O(2) or H(2) (18)O was a mixture of molecules containing up to three labeled oxygen atoms. Primary mass spectra of such mixtures were complex but were greatly simplified by tandem MS. This analysis indicated that the 6a oxygen of pisatin was derived from H(2)O and not from O(2). Labeling patterns for the other five oxygen atoms were consistent with the proposed pathway for biosynthesis of pisatin and related isoflavonoids. We conclude that the fungal hydroxylation of maackiain is catalyzed by an oxygenase, but the biosynthetic route to the 6a hydroxyl of pisatin is unknown.

Journal Article↗
PubMed1987

Hyperglucagonemia during insulin deficiency accelerates protein catabolism.

Hyperglucagonemia coexists with insulin deficiency or insulin resistance in many conditions where urinary nitrogen excretion is increased, but the precise role of glucagon in these conditions is controversial. The purpose of this study was to evaluate the effect of hyperglucagonemia on protein metabolism in insulin-deficient subjects. We used the stable isotope of an essential amino acid (L-[1-13C]leucine) as a tracer of in vivo protein metabolism. A combined deficiency of insulin and glucagon was induced by intravenous infusion of somatostatin. Hyperglucagonemia and hypoinsulinemia were induced by infusions of somatostatin and glucagon. When somatostatin alone was infused leucine flux increased, indicating a 6-17% increase in proteolysis. When somatostatin and glucagon were infused, leucine flux increased, indicating a 12-32% increase in proteolysis. The increase in leucine flux during the infusion of somatostatin and glucagon was higher than the increase during infusion of somatostatin alone. Somatostatin alone did not change leucine oxidation, whereas the somatostatin plus glucagon increased leucine oxidation 100%. We conclude that hyperglucagonemia accelerates proteolysis and leucine oxidation in insulin-deficient humans.

Adult↗
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

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↗