Search PubMed⌕ Search

Biomedical subjects

D M Bier

Publications and source records attributed to D M Bier.

At least 37 records · Page 2Linked to original sources
PubMed1995

Glutamine: a major gluconeogenic precursor and vehicle for interorgan carbon transport in man.

To compare glutamine and alanine as gluconeogenic precursors, we simultaneously measured their systemic turnovers, clearances, and incorporation into plasma glucose, their skeletal muscle uptake and release, and the proportion of their appearance in plasma directly due to their release from protein in postabsorptive normal volunteers. We infused the volunteers with [U-14C] glutamine, [3-13C] alanine, [2H5] phenylalanine, and [6-3H] glucose to isotopic steady state and used the forearm balance technique. We found that glutamine appearance in plasma exceeded that of alanine (5.76 +/- 0.26 vs. 4.40 +/- 0.33 mumol.kg-1.min-1, P < 0.001), while alanine clearance exceeded glutamine clearance (14.7 +/- 1.3 vs. 9.3 +/- 0.8 ml.kg-1.min-1, P < 0.001). Glutamine appearance in plasma directly due to its release from protein was more than double that of alanine (2.45 +/- 0.25 vs. 1.16 +/- 0.12 mumol.kg-1.min-1, P < 0.001). Although overall carbon transfer to glucose from glutamine and alanine was comparable (3.53 +/- 0.24 vs 3.47 +/- 0.32 atoms.kg-1.min-1), nearly twice as much glucose carbon came from protein derived glutamine than alanine (1.48 +/- 0.15 vs 0.88 +/- 0.09 atoms.kg-1.min-1, P < 0.01). Finally, forearm muscle released more glutamine than alanine (0.88 +/- 0.05 vs 0.48 +/- 0.05 mumol.100 ml-1.min-1, P < 0.01). We conclude that in postabsorptive humans glutamine is quantitatively more important than alanine for transporting protein-derived carbon through plasma and adding these carbons to the glucose pool.

Alanine↗
PubMed1995

Metabolic and clinical response to recombinant human insulin-like growth factor I in myotonic dystrophy--a clinical research center study.

Muscle weakness and wasting in myotonic dystrophy (MyD) are believed to be due to a decrease in muscle protein synthesis, secondary to insulin resistance. A 4-month, randomized, double blind, placebo-controlled trial was undertaken to assess whether recombinant human insulin-like growth factor I (rhIGF-I) may overcome the insulin resistance. Patients received either 5 mg rhIGF-I (n = 7) or placebo (n = 9), sc, twice daily. Glucose metabolism was assessed by stable label iv glucose tolerance test, amino acid metabolism by L-[13C] leucine turnover, body composition by dual energy x-ray absorptiometry and N excretion, and muscle response by manual muscle strength and neuromuscular function. In the treated group, the insulin sensitivity index, insulin action, and glucose disposal all increased (P < 0.05). Leucine flux and leucine incorporation into protein increased (P < 0.05), and the rate of leucine oxidation to leucine turnover decreased (P < 0.05), findings indicative of increased protein synthesis. Body weight and lean body mass increased, whereas percent body fat decreased (P < 0.05). An increase in manual muscle strength of 0.42 +/- 0.30 (P < 0.02) and in neuromuscular function of 17.5 +/- 11.7 (P < 0.02) occurred in the four patients who received a rhIGF-I dose greater than 70 micrograms/kg, whereas a more modest response occurred in the three patients who received a dose less than 70 micrograms/kg. Two patients showed dramatic improvement. Long term rhIGF-I therapy appears to cause metabolic and muscle improvement in optimally treated MyD patients.

Adult↗
PubMed1994

Determination of cortisol in human plasma by gas chromatography/negative ion chemical ionization/mass spectrometry.

We report an isotope dilution mass spectrometry method using capillary gas chromatography negative ion chemical ionization for the determination of cortisol in human plasma. Cortisol was derivatized with pentafluoropropionic anhydride at room temperature and measured by selected ion monitoring of the molecular ion. This method utilized d4-cortisol as an internal standard and required only a simple correction for the isotope contribution. A sensitivity as low as 0.02 pmol (s/n > 10) can be achieved easily. Therefore a plasma sample as small as 0.1 ml can be used for the accurate measurement of cortisol in humans.

Acetonitriles↗
PubMed1994

Growth hormone administration in older adults: effects on albumin synthesis.

Evidence suggests that the albumin gene contains a growth hormone (GH) responsive element. Our purpose was to determine if GH administration to older men increases the rate of albumin synthesis and whether this is related to the increase in nitrogen retention observed during short-term recombinant human GH (rhGH) administration. Five older men (60-75 yr) received daily injections (40 micrograms/kg) of rhGH for 2 wk, whereas four others received daily injections (10 micrograms/kg) for 4 wk. In both the 2- and 4-wk recipients, rhGH administration increased (P < 0.05) fasting plasma insulin-like growth factor I levels and reduced (P < 0.05) 24-h urinary nitrogen excretion. However, during an overnight fast, the fractional rate of albumin synthesis determined by the in vivo rate of incorporation of intravenously infused L-[1-13C]leucine into plasma albumin was unchanged after 2 or 4 wk of treatment. The average plasma albumin fractional synthetic rate was 8.6 +/- 0.6%/day before and 9.4 +/- 0.7%/day after rhGH treatment (P = 0.12). We conclude that short-term rhGH administration and the subsequent increase in urinary nitrogen retention does not result in an increase in the rate of plasma albumin synthesis in older men.

Aged↗
PubMed1993

No evidence for feedback inhibition of hepatic apolipoprotein B (apo B) production after extracorporeal low density lipoprotein precipitation as determined by [1-13C]leucine infusion in normal volunteers.

To determine the impact of an acute reduction of the circulating mass of apolipoprotein B (apo B) on apo B metabolism we studied six healthy male volunteers before (day 0), 1 day after (day 2), and 7 days after (day 8) an LDL apheresis treatment which reduced apo B mass by 59%. Appearance of newly synthesized apo B in plasma VLDL and LDL was studied using a primed-constant infusion of [1-13C]-leucine. VLDL apo B pool size and fractional VLDL apo B production rate calculated using a one-compartment model were similar on all 3 study days. Absolute VLDL apo B production was not statistically different throughout the study (19.7 +/- 12.3, 19.5 +/- 7.5, 29.1 +/- 17.7 mg kg-1 day-1). LDL apo B fractional production rate was increased on day 2 (0.38 +/- 0.17, 0.68 +/- 0.08, 0.37 +/- 0.06 pools day-1 on days 0, 2, and 8; P < 0.01). Absolute LDL apo B production, however, remained constant throughout the study (10.8 +/- 3.3, 11.0 +/- 1.9, 10.8 +/- 3.1 mg kg-1 day-1). We conclude that in healthy male volunteers acute reduction of the circulating apo B mass by LDL apheresis does not affect apo B metabolism significantly.

Adult↗
PubMed1993

Effects of protein restriction and acute refeeding on leucine and lysine kinetics in young men.

To explore the effects of altered protein intake on the uptake and utilization of dietary amino acids in human subjects, six healthy male Massachusetts Institute of Technology students were studied during three dietary periods each of 9 days, with tracer infusion studies conducted on days 8 and 9. During one period the diet provided a generous protein intake (1.5 g.kg-1.day-1) and during the other two a low-protein intake (0.1 g.kg-1.day-1). Tracer infusions (fed state) were given while subjects received either a liquid formula, supplying the prior protein intake or (on day 9) a generous intake. Combinations of [2H3]Leu and [13C]Leu and of [15N]Lys and [2H4]Lys were given via continuous intravenous or intragastric infusion for 4 h to estimate leucine kinetics and the first-pass splanchnic uptake of tracer. Dietary-induced changes in leucine flux and oxidation were similar irrespective of the tracer and/or route of administration and sampled pool (leucine or KIC) used for calculation. Estimates of absolute changes in the rates of leucine disappearance via nonoxidative metabolism (protein synthesis) and of appearance via protein breakdown depended on the route of [13C]Leu administration. However, it appears that both altered rates of protein synthesis and breakdown contribute to the adaptations required in the body nitrogen economy when protein intakes are restricted and subsequently resupplied. From the intragastric [13C]Leu protocol, the first-pass splanchnic uptake of tracer was the same (approximately 30%) for generous, low-protein, and refed conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Acute effects of resistance exercise on muscle protein synthesis rate in young and elderly men and women.

Muscle mass and function are improved in the elderly during resistance exercise training. These improvements must result from alterations in the rates of muscle protein synthesis and breakdown. We determined the rate of quadriceps muscle protein synthesis using the in vivo rate of incorporation of intravenously infused [13C]leucine into mixed-muscle protein in both young (24 yr) and elderly (63-66 yr) men and women before and at the end of 2 wk of resistance exercise training. Before training, the fractional rate of muscle protein synthesis was lower in the elderly than in the young (0.030 +/- 0.003 vs. 0.049 +/- 0.004%/h; P = 0.004) but increased (P < 0.03) to a comparable rate of muscle protein synthesis in both young (0.075 +/- 0.009%/h) and elderly subjects (0.076 +/- 0.011%/h) after 2 wk of exercise. In the elderly, muscle mass, 24-h urinary 3-methylhistidine and creatinine excretion, and whole body protein breakdown rate determined during the [13C]leucine infusion were not changed after 2 wk of exercise. These findings demonstrate that, during the initial phase of a resistance exercise training program, a marked increase in quadriceps muscle protein synthesis rate occurs in elderly and young adults without an increase in the rate of whole body protein breakdown. In the elderly, this was not accompanied by an increase in urinary 3-methylhistidine excretion, an index of myofibrillar protein breakdown.

Adult↗
PubMed1993

Effect of endurance training on plasma free fatty acid turnover and oxidation during exercise.

Plasma free fatty acid (FFA) levels tend to be lower and the plasma lipolytic hormone response to prolonged exercise of the same intensity is blunted after endurance exercise training. To determine whether training elicits a corresponding decrease in plasma FFA turnover and metabolism during prolonged exercise, we measured plasma [1-13C]palmitate kinetics and oxidation and respiratory gas exchange in 13 subjects during the latter portion of a 90- to 120-min bout of cycle ergometer work performed before and after 12 wk of alternate-day cycling and running. Training increased total fat oxidation during prolonged exercise by 41% (P < 0.005). However, for the final 30-60 min of the cycle ergometer protocol, the rate of 13CO2 production from [1-13C]palmitate oxidation was 27% lower (P < 0.05), the rate of palmitate turnover was 33% less (P < 0.05), and plasma FFA and glycerol concentrations were 32 and 20% lower (P < 0.05), respectively, than in the untrained state. Thus endurance exercise training results in decreased plasma FFA turnover and oxidation during a 90- to 120-min bout of submaximal exercise because of a slower rate of FFA release from adipose tissue.

Adult↗
PubMed1993

Short-term growth hormone treatment does not increase muscle protein synthesis in experienced weight lifters.

The purpose of this study was to determine whether recombinant human growth hormone (GH) administration enhances muscle protein anabolism in experienced weight lifters. The fractional rate of skeletal muscle protein synthesis and the whole body rate of protein breakdown were determined during a constant intravenous infusion of [13C]leucine in 7 young (23 +/- 2 yr; 86.2 +/- 4.6 kg) healthy experienced male weight lifters before and at the end of 14 days of subcutaneous GH administration (40 microgram.kg-1 x day-1). GH administration increased fasting serum insulin-like growth factor-I (from 224 +/- 20 to 589 +/- 80 ng/ml, P = 0.002) but did not increase the fractional rate of muscle protein synthesis (from 0.034 +/- 0.004 to 0.034 +/- 0.002%/h) or reduce the rate of whole body protein breakdown (from 103 +/- 4 to 108 +/- 5 mumol.kg-1 x h-1). These findings suggest that short-term GH treatment does not increase the rate of muscle protein synthesis or reduce the rate of whole body protein breakdown, metabolic alterations that would promote muscle protein anabolism in experienced weight lifters attempting to further increase muscle mass.

Adult↗
PubMed1993

The effect of hemodialysis on protein metabolism. A leucine kinetic study.

To assess the effect of hemodialysis on protein metabolism, leucine flux was measured in seven patients before, during, and after high efficiency hemodialysis using cuprophane dialyzers and bicarbonate dialysate during a primed-constant infusion of L-[1-13C]leucine. The kinetics [mumol/kg per h, mean +/- SD] are as follows: leucine appearance into the plasma leucine pool was 86 +/- 28, 80 +/- 28, and 85 +/- 25, respectively, before, during, and after dialysis. Leucine appearance into the whole body leucine pool, derived from plasma [1-13C]alpha-ketoisocaproate enrichment, was 118 +/- 31, 118 +/- 31, and 114 +/- 28 before, during, and after dialysis, respectively. In the absence of leucine intake, appearance rate reflects protein degradation, which was clearly unaffected by dialysis. Leucine oxidation rate was 17.3 +/- 7.8 before, decreased to 13.8 +/- 7.8 during, and increased to 18.9 +/- 10.3 after dialysis (P = 0.027). Leucine protein incorporation was 101 +/- 26 before, was reduced to 89 +/- 23 during, and returned to 95 +/- 23 after dialysis (P = 0.13). Leucine net balance, the difference between leucine protein incorporation and leucine release from endogenous degradation, was -17.3 +/- 7.8 before, decreased to -28.5 +/- 11.0 during, and returned to -18.9 +/- 10.3 after dialysis (P < 0.0001). This markedly more negative leucine balance during dialysis was accountable by dialysate leucine loss, which was 14.4 +/- 6.2 mumol/kg per h. These data suggest that hemodialysis using a cuprophane membrane did not acutely induce protein degradation. It was, nevertheless, a net catabolic event because protein synthesis was reduced and amino acid was lost into the dialysate.

Adult↗
PubMed1993

Effect of intravenous amino acids on protein metabolism of preterm infants during the first three days of life.

Twenty-three preterm infants with respiratory distress syndrome (mean birth weight 1.07 kg, SD 0.24 kg) were randomly assigned to receive glucose alone or glucose with amino acids (1.5 g.kg-1.d-1) i.v. beginning on the 1st d of life. Blood ammonia and serum urea, CO2 content, sodium, potassium, chloride, and ionized calcium concentrations were normal and did not differ between treatment groups. Nitrogen balance was significantly greater in the group that received amino acids [88 (SD 54) versus -135 (SD 45) mg.kg-1.d-1]. In 12 infants (seven, glucose-only; five, glucose and amino acids), leucine kinetic studies were also performed on the 3rd d of life. These 12 infants received a 4-h primed constant infusion of L-[1-13C]leucine. Blood and breath were collected and analyzed for [1-13C]ketoisocaproate and 13CO2, respectively. Leucine turnover and oxidation were calculated. Both leucine turnover and oxidation were significantly higher in the group receiving amino acids than in the glucose-only group [241 (SD 38) versus 164 (SD 25) mumol.kg-1.h-1 and 71 (SD 22) versus 40 (SD 17) mumol.kg-1.h-1, respectively]. In addition, the calculated rate of protein synthesis was higher in the group receiving amino acids [6.9 (SD 1.1) versus 5.0 (SD 1.2) g.kg-1.d-1]. These data indicate that the i.v. administration of amino acids (1.5 g.kg-1.d-1) to ill preterm infants beginning on the 1st d of life improves whole-body protein balance as a result of increased protein synthesis.

Amino Acids↗
PubMed1993

Effects of different plasma glucose concentrations on lipolytic and ketogenic responsiveness to epinephrine in type I (insulin-dependent) diabetic subjects.

The effects of two different plasma glucose concentrations (5 and 10 mmol/L) on lipolysis and ketogenesis during baseline and in response to epinephrine infusion were evaluated in insulin-dependent diabetic patients. Each insulin-dependent diabetic subject was studied during euglycemia, hyperglycemia with hypoinsulinemia, and hyperglycemia with hyperinsulinemia. Total ketone body (TKB) concentrations were significantly higher in hyperglycemic-hypoinsulinemic diabetics than in hyperglycemic-hyperinsulinemic and normoglycemic diabetics. Hyperglycemic-hyperinsulinemics had higher TKB concentrations than euglycemic diabetics. During epinephrine infusion, the ketone body rate of appearance and concentration significantly increased in all groups. Plasma FFA concentrations were significantly higher in hyperglycemic-hypoinsulinemic diabetics than in the other groups. During epinephrine infusion, the plasma FFA rate of appearance and concentration significantly increased in all groups. The apparent fraction of FFA converted to ketones was increased by epinephrine in all groups, except in hyperglycemic-hyperinsulinemic diabetics. In conclusion, this study demonstrates that although insulin alone decreases FFA and TKB concentrations, it does not affect the fraction of FFA converted to ketones. If hyperinsulinemia is superimposed on hyperglycemia, there is both a reduction of ketogenesis capacity, compared to hyperglycemia alone, and a decrease in the apparent fraction of FFA converted to ketone bodies.

Adult↗
PubMed1992

Measurement of muscle protein fractional synthetic rate by capillary gas chromatography/combustion isotope ratio mass spectrometry.

The measurement of skeletal muscle protein fractional synthetic rate using an infusion of (1-13C)leucine and measuring the isotopic abundance of the tracer in skeletal muscle protein by preparative gas chromatography (GC)/ninhydrin isotope ratio mass spectrometry (IRMS) is laborious and subject to errors owing to contamination by 12C. The purpose of this study was to compare muscle (13C)leucine enrichment measured with the conventional preparative GC/ninhydrin IRMS approach to a new, continuous-flow technique using capillary GC/combustion IRMS. Quadriceps muscles were removed from four Sprague-Dawley rats after each was infused at a different rate with (1-13C)leucine for 6-8 h. Muscle leucine enrichment (at. % excess) measured by both methods differed by less than 4%, except at low (13C)leucine enrichments (less than 0.03 at. % excess). In addition, capillary GC/combustion IRMS was used to assess muscle (13C)leucine enrichment and fractional muscle protein synthesis rate in ten normal young men and women infused with (1,2-13C2)leucine for 12-14 h. This approach reduced the variability of the isotope abundance measure and gave estimates of muscle protein synthesis rate (0.050 +/- 0.011% h-1 (mean +/- SEM); range = 0.023-0.147% h-1) that agree with published values determined using the standard analytical approach. The measurement of (13C)leucine enrichment from skeletal muscle protein by capillary GC/combustion IRMS provides a simple, acceptable and practical alternative to preparative GC/ninhydrin IRMS.

Adult↗
PubMed1992

Effect of growth hormone and resistance exercise on muscle growth in young men.

The purpose of this study was to determine whether growth hormone (GH) administration enhances the muscle anabolism associated with heavy-resistance exercise. Sixteen men (21-34 yr) were assigned randomly to a resistance training plus GH group (n = 7) or to a resistance training plus placebo group (n = 9). For 12 wk, both groups trained all major muscle groups in an identical fashion while receiving 40 micrograms recombinant human GH.kg-1.day-1 or placebo. Fat-free mass (FFM) and total body water increased (P less than 0.05) in both groups but more (P less than 0.01) in the GH recipients. Whole body protein synthesis rate increased more (P less than 0.03), and whole body protein balance was greater (P = 0.01) in the GH-treated group, but quadriceps muscle protein synthesis rate, torso and limb circumferences, and muscle strength did not increase more in the GH-treated group. In the young men studied, resistance exercise with or without GH resulted in similar increments in muscle size, strength, and muscle protein synthesis, indicating that 1) the larger increase in FFM with GH treatment was probably due to an increase in lean tissue other than skeletal muscle and 2) resistance training supplemented with GH did not further enhance muscle anabolism and function.

Adipose Tissue↗