scholarly journals Amino acids and insulin are both required to regulate assembly of the eIF4E · eIF4G complex in rat skeletal muscle

2001 ◽  
Vol 281 (3) ◽  
pp. E565-E574 ◽  
Author(s):  
Michele Balage ◽  
Sandrine Sinaud ◽  
Magali Prod'Homme ◽  
Dominique Dardevet ◽  
Thomas C. Vary ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Protein Meal ◽  
Acid Protein ◽  
Postprandial Insulin ◽  
Amino Acid Protein

The respective roles of insulin and amino acids in regulation of skeletal muscle protein synthesis and degradation after feeding were examined in rats fasted for 17 h and refed over 1 h with either a 25 or a 0% amino acid/protein meal. In each nutritional condition, postprandial insulin secretion was either maintained (control groups: C25 and C0) or blocked with diazoxide injections (diazoxide groups: DZ25 and DZ0). Muscle protein metabolism was examined in vitro in epitrochlearis muscles. Only feeding the 25% amino acid/protein meal in the presence of increased plasma insulin concentration (C25 group) stimulated protein synthesis and inhibited proteolysis in skeletal muscle compared with the postabsorptive state. The stimulation of protein synthesis was associated with increased phosphorylation of eukaryotic initiation factor (eIF)4E binding protein-1 (4E-BP1), reduced binding of eIF4E to 4E-BP1, and increased assembly of the active eIF4E · eIF4G complex. The p70 S6 kinase (p70S6k) was also hyperphosphorylated in response to the 25% amino acid/protein meal. Acute postprandial insulin deficiency induced by diazoxide injections totally abolished these effects. Feeding the 0% amino acid/protein meal with or without postprandial insulin deficiency did not stimulate muscle protein synthesis, reduce proteolysis, or regulate initiation factors and p70S6kcompared with fasted rats. Taken together, our results suggest that both insulin and amino acids are required to stimulate protein synthesis, inhibit protein degradation, and regulate the interactions between eIF4E and 4E-BP1 or eIF4G in response to feeding.

scholarly journals Testosterone injection stimulates net protein synthesis but not tissue amino acid transport

1998 ◽  
Vol 275 (5) ◽  
pp. E864-E871 ◽  
Author(s):  
Arny A. Ferrando ◽  
Kevin D. Tipton ◽  
David Doyle ◽  
Stuart M. Phillips ◽  
Joaquin Cortiella ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Amino Acid Transport ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Acid Transport ◽  
Skeletal Muscle Protein ◽  
Net Protein

Testosterone administration (T) increases lean body mass and muscle protein synthesis. We investigated the effects of short-term T on leg muscle protein kinetics and transport of selected amino acids by use of a model based on arteriovenous sampling and muscle biopsy. Fractional synthesis (FSR) and breakdown (FBR) rates of skeletal muscle protein were also directly calculated. Seven healthy men were studied before and 5 days after intramuscular injection of 200 mg of testosterone enanthate. Protein synthesis increased twofold after injection ( P < 0.05), whereas protein breakdown was unchanged. FSR and FBR calculations were in accordance, because FSR increased twofold ( P < 0.05) without a concomitant change in FBR. Net balance between synthesis and breakdown became more positive with both methodologies ( P< 0.05) and was not different from zero. T injection increased arteriovenous essential and nonessential nitrogen balance across the leg ( P < 0.05) in the fasted state, without increasing amino acid transport. Thus T administration leads to an increased net protein synthesis and reutilization of intracellular amino acids in skeletal muscle.

Combined effects of hyperaminoacidemia and oxandrolone on skeletal muscle protein synthesis

2000 ◽  
Vol 278 (2) ◽  
pp. E273-E279 ◽  
Author(s):  
Melinda Sheffield-Moore ◽  
Robert R. Wolfe ◽  
Dennis C. Gore ◽  
Steven E. Wolf ◽  
Dennis M. Ferrer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Compartment Model ◽  
Acid Mixture ◽  
Skeletal Muscle Protein ◽  
Amino Acid Infusion

We investigated whether the normal anabolic effects of acute hyperaminoacidemia were maintained after 5 days of oxandrolone (Oxandrin, Ox)-induced anabolism. Five healthy men [22 ± 3 (SD) yr] were studied before and after 5 days of oral Ox (15 mg/day). In each study, a 5-h basal period was followed by a 3-h primed-continuous infusion of a commercial amino acid mixture (10% Travasol). Stable isotopic data from blood and muscle sampling were analyzed using a three-compartment model to calculate muscle protein synthesis and breakdown. Model-derived muscle protein synthesis increased after amino acid infusion in both the control [basal control (BC) vs. control + amino acids (C+AA); P < 0.001] and Ox study [basal Ox (BOx) vs. Ox + amino acids (Ox+AA); P < 0.01], whereas protein breakdown was unchanged. Fractional synthetic rates of muscle protein increased 94% (BC vs. C+AA; P = 0.01) and 53% (BOx vs. Ox+AA; P < 0.01), respectively. We conclude that the normal anabolic effects of acute hyperaminoacidemia are maintained in skeletal muscle undergoing oxandrolone-induced anabolism.

Response of rat heart and skeletal muscle protein in vivo to insulin and amino acid infusion

1993 ◽  
Vol 264 (6) ◽  
pp. E958-E965 ◽  
Author(s):  
P. H. McNulty ◽  
L. H. Young ◽  
E. J. Barrett
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Skeletal Muscle Protein ◽  
Acid Infusion ◽  
Amino Acid Infusion

Whether insulin, at physiological concentrations, stimulates net muscle protein synthesis in vivo remains unresolved. To examine this, we infused either saline, insulin (2.8 mU.kg-1.min-1, euglycemic clamp), an amino acid solution, or insulin plus amino acids for 4 h into awake overnight-fasted rats. Heart and skeletal muscle protein synthesis was measured by either a continuous tracer infusion method, using L-[1-14C]leucine, L-[2,5-3H]leucine, or L-[ring-2,6-3H]phenylalanine or by injection of L-[ring-2,6-3H]phenylalanine with a pool-flooding bolus of unlabeled phenylalanine. In heart, synthesis rates obtained using the arterial plasma specific activity of [3H]phenylalanine administered as either a tracer infusion or flooding bolus were comparable in saline-treated rats (range 10.9 +/- 1.2 to 12.2 +/- 0.9%/day) and were not affected by infusion of insulin or amino acids. Estimates using continuous infusion of L-[1-14C]leucine were significantly lower (P < 0.001), except when unlabeled amino acids were given also. In skeletal muscle, rates estimated using the flooding bolus (6.7 +/- 0.8%/day) were also not affected by insulin or amino acids. Estimates using continuous infusion of [3H]leucine (2.6 +/- 0.3%/day) or [3H]phenylalanine (2.8 +/- 1.0%/day) were lower and were still lower using [14C]leucine (1.6 +/- 0.6%/day), but increased toward those estimated with the flooding bolus during amino acid infusion. We conclude that, in heart muscle of the mature rat in vivo, neither insulin nor amino acids affect protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino acids augment muscle protein synthesis in neonatal pigs during acute endotoxemia by stimulating mTOR-dependent translation initiation

2007 ◽  
Vol 293 (5) ◽  
pp. E1416-E1425 ◽  
Author(s):  
Renán A. Orellana ◽  
Asumthia Jeyapalan ◽  
Jeffery Escobar ◽  
Jason W. Frank ◽  
Hanh V. Nguyen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Translation Initiation ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Neonatal Pigs

In skeletal muscle of adults, sepsis reduces protein synthesis by depressing translation initiation and induces resistance to branched-chain amino acid stimulation. Normal neonates maintain a high basal muscle protein synthesis rate that is sensitive to amino acid stimulation. In the present study, we determined the effect of amino acids on protein synthesis in skeletal muscle and other tissues in septic neonates. Overnight-fasted neonatal pigs were infused with endotoxin (LPS, 0 and 10 μg·kg−1·h−1), whereas glucose and insulin were maintained at fasting levels; amino acids were clamped at fasting or fed levels. In the presence of fasting insulin and amino acids, LPS reduced protein synthesis in longissimus dorsi (LD) and gastrocnemius muscles and increased protein synthesis in the diaphragm, but had no effect in masseter and heart muscles. Increasing amino acids to fed levels accelerated muscle protein synthesis in LD, gastrocnemius, masseter, and diaphragm. LPS stimulated protein synthesis in liver, lung, spleen, pancreas, and kidney in fasted animals. Raising amino acids to fed levels increased protein synthesis in liver of controls, but not LPS-treated animals. The increase in muscle protein synthesis in response to amino acids was associated with increased mTOR, 4E-BP1, and S6K1 phosphorylation and eIF4G-eIF4E association in control and LPS-infused animals. These findings suggest that amino acids stimulate skeletal muscle protein synthesis during acute endotoxemia via mTOR-dependent ribosomal assembly despite reduced basal protein synthesis rates in neonatal pigs. However, provision of amino acids does not further enhance the LPS-induced increase in liver protein synthesis.

scholarly journals Inverse Regulation of Protein Turnover and Amino Acid Transport in Skeletal Muscle of Hypercatabolic Patients

2002 ◽  
Vol 87 (7) ◽  
pp. 3378-3384 ◽  
Author(s):  
Gianni Biolo ◽  
R. Y. Declan Fleming ◽  
Sergio P. Maggi ◽  
Thuan T. Nguyen ◽  
David N. Herndon ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Protein Degradation ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Transmembrane Transport ◽  
Protein Breakdown ◽  
Balance Technique

We have investigated the relationships between the rates of muscle protein synthesis and degradation and of transmembrane transport of selected amino acids in leg skeletal muscle of 19 severely burned patients and 18 normal controls in the postabsorptive state. Patients were studied on the 14 ± 5 postburn day, and their mean burn size was 66% ± 18% of total body surface area. Methods were based on the leg arteriovenous balance technique in combination with biopsies of the vastus lateralis muscle and infusions of isotopic tracers of amino acids. Net muscle protein breakdown was greater in the patients because of an 83% increase in the rate of muscle protein degradation. The rate of muscle protein synthesis was also increased in the patients but to a lesser extent than protein degradation, i.e. by 50% with the arteriovenous phenylalanine balance technique and by 49% with the direct tracer incorporation method. The absolute values of inward transport of phenylalanine, leucine, and lysine were not significantly different in the two groups. However, the ability of transport systems to take up amino acids from the bloodstream, as assessed by dividing inward transport by amino acid delivery to leg muscle, were 50–63% lower in the patients. In contrast, outward phenylalanine and lysine transport were 40% and 67% greater in the patients than in the controls, respectively. We conclude the primary alteration in muscle protein metabolism is an acceleration of protein breakdown, and the increase in protein synthesis likely is due to increased intracellular amino acid availability as a result of accelerated breakdown. Transmembrane transport in the outward direction is accelerated, presumably to facilitate the export of amino acids from muscle to other tissues. In contrast, transmembrane transport in the inward direction is impaired relatively to the increased delivery of circulating amino acid to skeletal muscle secondary to accelerated blood flow.

Growth hormone acutely stimulates forearm muscle protein synthesis in normal humans

1991 ◽  
Vol 260 (3) ◽  
pp. E499-E504 ◽  
Author(s):  
D. A. Fryburg ◽  
R. A. Gelfand ◽  
E. J. Barrett
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Growth Hormone ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Skeletal Muscle Protein ◽  
Skeletal Muscle Protein Synthesis ◽  
Igf I ◽  
Normal Humans

The short-term effects of growth hormone (GH) on skeletal muscle protein synthesis and degradation in normal humans are unknown. We studied seven postabsorptive healthy men (age 18-23 yr) who received GH (0.014 micrograms.kg-1.min-1) via intrabrachial artery infusion for 6 h. The effects of GH on forearm amino acid and glucose balances and on forearm amino acid kinetics [( 3H]Phe and [14C]Leu) were determined after 3 and 6 h of the GH infusion. Forearm deep vein GH rose to 35 +/- 6 ng/ml in response to GH, whereas systemic levels of GH, insulin, and insulin-like growth factor I (IGF-I) were unchanged. Forearm glucose uptake did not change during the study. After 6 h, GH suppressed forearm net release (3 vs. 6 h) of Phe (P less than 0.05), Leu (P less than 0.01), total branched-chain amino acids (P less than 0.025), and essential neutral amino acids (0.05 less than P less than 0.1). The effect on the net balance of Phe and Leu was due to an increase in the tissue uptake for Phe (71%, P less than 0.05) and Leu (37%, P less than 0.005) in the absence of any significant change in release of Phe or Leu from tissue. In the absence of any change in systemic GH, IGF-I, or insulin, these findings suggest that locally infused GH stimulates skeletal muscle protein synthesis. These findings have important physiological implications for both the role of daily GH pulses and the mechanisms through which GH can promote protein anabolism.

An abundant supply of amino acids enhances the metabolic effect of exercise on muscle protein

1997 ◽  
Vol 273 (1) ◽  
pp. E122-E129 ◽  
Author(s):  
G. Biolo ◽  
K. D. Tipton ◽  
S. Klein ◽  
R. R. Wolfe
Keyword(s):  
Amino Acids ◽  
Blood Flow ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Amino Acid Mixture ◽  
Acid Mixture ◽  
Protein Kinetics ◽  
Amino Acid Infusion

Six normal untrained men were studied during the intravenous infusion of a balanced amino acid mixture (approximately 0.15 g.kg-1.h-1 for 3 h) at rest and after a leg resistance exercise routine to test the influence of exercise on the regulation of muscle protein kinetics by hyperaminoacidemia. Leg muscle protein kinetics and transport of selected amino acids (alanine, phenylalanine, leucine, and lysine) were isotopically determined using a model based on arteriovenous blood samples and muscle biopsy. The intravenous amino acid infusion resulted in comparable increases in arterial amino acid concentrations at rest and after exercise, whereas leg blood flow was 64 +/- 5% greater after exercise than at rest. During hyperaminoacidemia, the increases in amino acid transport above basal were 30-100% greater after exercise than at rest. Increases in muscle protein synthesis were also greater after exercise than at rest (291 +/- 42% vs. 141 +/- 45%). Muscle protein breakdown was not significantly affected by hyperminoacidemia either at rest or after exercise. We conclude that the stimulatory effect of exogenous amino acids on muscle protein synthesis is enhanced by prior exercise, perhaps in part because of enhanced blood flow. Our results imply that protein intake immediately after exercise may be more anabolic than when ingested at some later time.

Suppression of muscle protein turnover and amino acid degradation by dietary protein deficiency

1992 ◽  
Vol 263 (2) ◽  
pp. E317-E325 ◽  
Author(s):  
N. E. Tawa ◽  
A. L. Goldberg
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Dietary Protein ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Normal Diet ◽  
High Rate ◽  
Acid Uptake ◽  
Rapid Weight Gain

To define the adaptations that conserve amino acids and muscle protein when dietary protein intake is inadequate, rats (60-70 g final wt) were fed a normal or protein-deficient (PD) diet (18 or 1% lactalbumin), and their muscles were studied in vitro. After 7 days on the PD diet, both protein degradation and synthesis fell 30-40% in skeletal muscles and atria. This fall in proteolysis did not result from reduced amino acid supply to the muscle and preceded any clear decrease in plasma amino acids. Oxidation of branched-chain amino acids, glutamine and alanine synthesis, and uptake of alpha-aminoisobutyrate also fell by 30-50% in muscles and adipose tissue of PD rats. After 1 day on the PD diet, muscle protein synthesis and amino acid uptake decreased by 25-40%, and after 3 days proteolysis and leucine oxidation fell 30-45%. Upon refeeding with the normal diet, protein synthesis also rose more rapidly (+30% by 1 day) than proteolysis, which increased significantly after 3 days (+60%). These different time courses suggest distinct endocrine signals for these responses. The high rate of protein synthesis and low rate of proteolysis during the first 3 days of refeeding a normal diet to PD rats contributes to the rapid weight gain ("catch-up growth") of such animals.

scholarly journals Amino acid infusion increases the sensitivity of muscle protein synthesis in vivo to insulin. Effect of branched-chain amino acids

1988 ◽  
Vol 254 (2) ◽  
pp. 579-584 ◽  
Author(s):  
P J Garlick ◽  
I Grant
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Branched Chain Amino Acids ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Branched Chain

Rates of muscle protein synthesis were measured in vivo in tissues of post-absorptive young rats that were given intravenous infusions of various combinations of insulin and amino acids. In the absence of amino acid infusion, there was a steady rise in muscle protein synthesis with plasma insulin concentration up to 158 mu units/ml, but when a complete amino acids mixtures was included maximal rates were obtained at 20 mu units/ml. The effect of the complete mixture could be reproduced by a mixture of essential amino acids or of branched-chain amino acids, but not by a non-essential mixture, alanine, methionine or glutamine. It is concluded that amino acids, particularly the branched-chain ones, increase the sensitivity of muscle protein synthesis to insulin.

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