Maintaining muscle protein anabolism after a metabolic stress: role of dextrose vs. amino acid availability

1997 ◽  
Vol 272 (1) ◽  
pp. E36-E44 ◽  
Author(s):  
M. J. Borel ◽  
P. E. Williams ◽  
K. Jabbour ◽  
J. C. Hibbard ◽  
P. J. Flakoll
Keyword(s):  
Muscle Protein ◽  
Nitrogen Loss ◽  
Metabolic Stress ◽  
Whole Body ◽  
Skeletal Muscle Protein ◽  
Protein Loss ◽  
Fasting Period ◽  
Amino Acid Availability ◽  
Hindlimb Muscle ◽  
Parenteral Infusions

The effect of chronic hypocaloric parenteral infusions of amino acids (AA) vs. dextrose (D) on protein homeostasis after a generalized metabolic stress was examined. Multicatheterized mongrel dogs were metabolically challenged by a 4-day fast and then administered a 4-day intravenous infusion of saline (S, n = 8), D (n = 8), or isocaloric AA (n = 7). Although nitrogen balance (g.kg.1.day-1) was similarly negative with S (-0.37 +/- 0.05), D (-0.28 +/- 0.03), and AA (-0.37 +/- 0.04) during the fasting period, it was less negative (P < or = 0.05) with AA (-0.06 +/- 0.04) than with D (-0.20 +/- 0.03) or S (-0.23 +/- 0.04) during nutrient infusion. AA resulted in net hindlimb uptake and D in net hindlimb release of essential AA (570 +/- 261 vs. -248 +/- 59 nmol.kg-1.min-1). Whereas S and D infusions led to net hindlimb muscle protein loss (-37 +/- 24 and -89 +/- 33 micrograms.kg-1.min-1, respectively, P < or = 0.05 vs. AA), parenteral AA resulted in net deposition (169 +/- 62 micrograms.kg-1.min-1) as measured using L-[ring-2H5]phenylalanine. Thus hypocaloric parenteral D infusion after a metabolic stress does not favor nitrogen conservation, because net whole body nitrogen loss, skeletal muscle protein catabolism, and hindlimb AA release were not blunted compared with S infusion. Conversely, hypocaloric AA infusion preserves whole body and muscle protein stores.

scholarly journals Growth Hormone, Alone and in Combination With Insulin, Increases Whole Body and Skeletal Muscle Protein Kinetics in Cancer Patients After Surgery

1999 ◽  
Vol 229 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Russell S. Berman ◽  
Lawrence E. Harrison ◽  
David B. Pearlstone ◽  
Michael Burt ◽  
Murray F. Brennan
Keyword(s):  
Skeletal Muscle ◽  
Growth Hormone ◽  
Cancer Patients ◽  
Muscle Protein ◽  
Whole Body ◽  
Skeletal Muscle Protein ◽  
Protein Kinetics

Do nonesterified fatty acids regulate skeletal muscle protein turnover in humans?

1993 ◽  
Vol 265 (3) ◽  
pp. E357-E361 ◽  
Author(s):  
M. Walker ◽  
E. Shmueli ◽  
S. E. Daley ◽  
B. G. Cooper ◽  
K. G. Alberti
Keyword(s):  
Skeletal Muscle ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Serum Insulin ◽  
Whole Body ◽  
Nonesterified Fatty Acid ◽  
Elevated Plasma ◽  
Skeletal Muscle Protein ◽  
Plasma Nefa ◽  
Nonesterified Fatty Acids

We examined whether elevated plasma nonesterified fatty acid (NEFA) levels exert a direct effect on protein metabolism by measuring [2H5]phenylalanine skeletal muscle exchange and whole body turnover. [2H5]phenylalanine was infused (0.5 mg.kg-1 x h-1) for 300 min in seven healthy subjects on two occasions. Intralipid (10%; 30 ml/h) or 0.154 mol/l NaCl was infused in random order from 120 min. Measurements were taken during basal (90-120 min) and infusion (270-300 min) periods. Intralipid infusion increased plasma NEFA levels [1.31 +/- 0.13 vs. 0.49 +/- 0.05 (SE) mmol/l; P < 0.05] and forearm NEFA uptake [45 +/- 76 vs. -51 +/- 44 nmol . 100 ml forearm-1 x min-1; P < 0.05]. Serum insulin and blood ketone body levels were similar with the two treatments. Elevated plasma NEFA levels were associated with a comparable decrease in forearm phenylalanine uptake (11 +/- 2 vs. 17 +/- 2 nmol x 100 ml forearm-1 x min-1; lipid vs. control, P < 0.05) and release (20 +/- 2 vs. 26 +/- 3 nmol x 100 ml forearm-1 x min-1; lipid vs. control, P < 0.05). However, there were no significant changes in net forearm phenylalanine exchange and whole body phenylalanine turnover. Therefore, elevated plasma NEFA levels were associated with a comparable decrease in the rates of skeletal muscle protein synthesis and breakdown but did not appear to influence overall protein balance, as assessed using [2H5]phenylalanine.

Protein Metabolism and Age: Influence of Insulin and Resistance Exercise

2001 ◽  
Vol 11 (s1) ◽  
pp. S150-S163 ◽  
Author(s):  
Peter A. Farrell
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Resistance Exercise ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mrna Translation ◽  
Bed Rest ◽  
Skeletal Muscle Protein ◽  
Amino Acid Availability ◽  
Effects Of Aging

Skeletal muscle proteins are constantly being synthesized and degraded, and the net balance between synthesis and degradation determines the resultant muscle mass. Biochemical pathways that control protein synthesis are complex, and the following must be considered: gene transcription, mRNA splicing, and transport to the cytoplasm; specific amino acyl-tRNA, messenger (mRNA), ribosomal (rRNA) availability; amino acid availability within the cell; the hormonal milieu; rates of mRNA translation; packaging in vesicles for some types of proteins; and post-translational processing such as glycation and phosphorylation/dephosphorylation. Each of these processes is responsive to the need for greater or lesser production of new proteins, and many states such as sepsis, uncontrolled diabetes, prolonged bed-rest, aging, chronic alcohol treatment, and starvation cause marked reductions in rates of skeletal muscle protein synthesis. In contrast, acute and chronic resistance exercise cause elevations in rates of muscle protein synthesis above rates found in nondiseased rested organisms, which are normally fed. Resistance exercise may be unique in this capacity. This chapter focuses on studies that have used exercise to elucidate mechanisms that explain elevations in rates of protein synthesis. Very few studies have investigated the effects of aging on these mechanisms; however, the literature that is available is reviewed.

Leucine as a regulator of whole body and skeletal muscle protein metabolism in humans

1992 ◽  
Vol 263 (5) ◽  
pp. E928-E934 ◽  
Author(s):  
K. S. Nair ◽  
R. G. Schwartz ◽  
S. Welle
Keyword(s):  
Amino Acids ◽  
Protein Degradation ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Plasma Concentrations ◽  
Essential Amino Acids ◽  
Whole Body ◽  
Skeletal Muscle Protein ◽  
Muscle Protein Metabolism

Leucine has been proposed as an in vivo regulator of protein metabolism, although the evidence for this in humans remains inconclusive. To test this hypothesis, we infused either L-leucine (154 +/- 1 mumol.kg-1 x h-1) or saline intravenously in six healthy men in two separate studies. L-Leucine infusion increased plasma concentrations of leucine and alpha-ketoisocaproate from 112 +/- 6 and 38 +/- 3 mumol/l to 480 +/- 27 (P < 0.001) and 94 +/- 13 mumol/l (P < 0.001), respectively, without any significant change in circulating insulin or C peptide levels. Leucine infusion decreased plasma concentrations of several amino acids and decreased whole body valine flux and valine oxidation (using L-[1-13C]valine as a tracer) and phenylalanine flux (using [2H5]-phenylalanine as a tracer). According to arteriovenous differences across the leg, the net balance of phenylalanine, valine, and lysine shifted toward greater retention during leucine infusion, whereas alanine balance did not change. Valine release and phenylalanine release from the leg (estimated from the dilution of respective tracers) decreased, indicating inhibition of protein degradation by leucine infusion. We conclude that leucine decreases protein degradation in humans and that this decreased protein degradation during leucine infusion contributes to the decrease in plasma essential amino acids. This study suggests a potential role for leucine as a regulator of protein metabolism in humans.

Prolonged bed rest decreases skeletal muscle and whole body protein synthesis

1996 ◽  
Vol 270 (4) ◽  
pp. E627-E633 ◽  
Author(s):  
A. A. Ferrando ◽  
H. W. Lane ◽  
C. A. Stuart ◽  
J. Davis-Street ◽  
R. R. Wolfe
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Bed Rest ◽  
Whole Body ◽  
Protein Breakdown ◽  
Skeletal Muscle Protein ◽  
Model Calculations ◽  
Body Protein

We sought to determine the extent to which the loss of lean body mass and nitrogen during inactivity was due to alterations in skeletal muscle protein metabolism. Six male subjects were studied during 7 days of diet stabilization and after 14 days of stimulated microgravity (-6 degrees bed rest). Nitrogen balance became more negative (P < 0.03) during the 2nd wk of bed rest. Leg and whole body lean mass decreased after bed rest (P < 0.05). Serum cortisol, insulin, insulin-like growth factor I, and testosterone values did not change. Arteriovenous model calculations based on the infusion of L-[ring-13C6]-phenylalanine in five subjects revealed a 50% decrease in muscle protein synthesis (PS; P < 0.03). Fractional PS by tracer incorporation into muscle protein also decreased by 46% (P < 0.05). The decrease in PS was related to a corresponding decrease in the sum of intracellular amino acid appearance from protein breakdown and inward transport. Whole body protein synthesis determined by [15N]alanine ingestion on six subjects also revealed a 14% decrease (P < 0.01). Neither model-derived nor whole body values for protein breakdown change significantly. These results indicate that the loss of body protein with inactivity is predominantly due to a decrease in muscle PS and that this decrease is reflected in both whole body and skeletal muscle measures.

scholarly journals Response of skeletal muscle protein synthesis to insulin in suckling pigs decreases with development

1998 ◽  
Vol 275 (4) ◽  
pp. E602-E609 ◽  
Author(s):  
Diane Wray-Cahen ◽  
Hanh V. Nguyen ◽  
Douglas G. Burrin ◽  
Philip R. Beckett ◽  
Marta L. Fiorotto ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Whole Body ◽  
Skeletal Muscle Protein ◽  
Protein Deposition ◽  
Skeletal Muscle Protein Synthesis ◽  
Elevated Rate

The elevated rate of muscle protein deposition in the neonate is largely due to an enhanced stimulation of skeletal muscle protein synthesis by feeding. To examine the role of insulin in this response, hyperinsulinemic-euglycemic-amino acid clamps were performed in 7- and 26-day-old pigs. Pigs were infused with 0, 30, 100, or 1,000 ng ⋅ kg−0.66 ⋅ min−1of insulin to mimic the plasma insulin levels observed under fasted, fed, refed, and supraphysiological conditions, respectively. Whole body amino acid disposal was determined from the rate of infusion of an amino acid mixture necessary to maintain plasma essential amino acid concentrations near their basal fasting levels. A flooding dose ofl-[4-3H]phenylalanine was used to measure skeletal muscle protein synthesis. Whole body amino acid disposal increased progressively as the insulin infusion rate increased, and this response was greater in 7- than in 26-day-old pigs. Skeletal muscle protein synthesis was stimulated by insulin, and this response was maximal at a low insulin infusion rate (30 ng ⋅ kg−0.66 ⋅ min−1). The stimulation of muscle protein synthesis by insulin was also greater in 7- than in 26- day-old pigs. These data suggest that muscle protein synthesis is more sensitive to insulin than whole body amino acid disposal. The results further suggest that insulin is a central regulatory factor in the elevated rate of muscle protein deposition and the increased response of skeletal muscle protein synthesis to feeding in the neonate.

Smoking impairs muscle protein synthesis and increases the expression of myostatin and MAFbx in muscle

2007 ◽  
Vol 293 (3) ◽  
pp. E843-E848 ◽  
Author(s):  
Anne Marie Winther Petersen ◽  
Faidon Magkos ◽  
Philip Atherton ◽  
Anna Selby ◽  
Kenneth Smith ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Inflammatory Markers ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Whole Body ◽  
Synthesis Process ◽  
Skeletal Muscle Protein ◽  
Expression Of Genes ◽  
Tnf Α

Smoking causes multiple organ dysfunction. The effect of smoking on skeletal muscle protein metabolism is unknown. We hypothesized that the rate of skeletal muscle protein synthesis is depressed in smokers compared with non-smokers. We studied eight smokers (≥20 cigarettes/day for ≥20 years) and eight non-smokers matched for sex (4 men and 4 women per group), age (65 ± 3 and 63 ± 3 yr, respectively; means ± SEM) and body mass index (25.9 ± 0.9 and 25.1 ± 1.2 kg/m2, respectively). Each subject underwent an intravenous infusion of stable isotope-labeled leucine in conjunction with blood and muscle tissue sampling to measure the mixed muscle protein fractional synthesis rate (FSR) and whole body leucine rate of appearance (Ra) in plasma (an index of whole body proteolysis), the expression of genes involved in the regulation of muscle mass (myostatin, a muscle growth inhibitor, and MAFBx and MuRF-1, which encode E3 ubiquitin ligases in the proteasome proteolytic pathway) and that for the inflammatory cytokine TNF-α in muscle, and the concentration of inflammatory markers in plasma (C-reactive protein, TNF-α, interleukin-6) which are associated with muscle wasting in other conditions. There were no differences between nonsmokers and smokers in plasma leucine concentration, leucine rate of appearance, and plasma concentrations of inflammatory markers, or TNF-α mRNA in muscle, but muscle protein FSR was much less (0.037 ± 0.005 vs. 0.059 ± 0.005%/h, respectively, P = 0.004), and myostatin and MAFBx (but not MuRF-1) expression were much greater (by ∼33 and 45%, respectivley, P < 0.05) in the muscle of smokers than of nonsmokers. We conclude that smoking impairs the muscle protein synthesis process and increases the expression of genes associated with impaired muscle maintenance; smoking therefore likely increases the risk of sarcopenia.

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