scholarly journals SPECIFICITY OF CREATINE IN THE CONTROL OF MUSCLE PROTEIN SYNTHESIS

1974 ◽  
Vol 62 (1) ◽  
pp. 145-151 ◽  
Author(s):  
Joanne S. Ingwall ◽  
Cynthia D. Weiner ◽  
Manuel F. Morales ◽  
Elaine Davis ◽  
Frank E. Stockdale
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Creatine ◽  
Embryonic Muscle ◽  
Chain Synthesis

This study provides additional evidence that creatine, an end product of contraction unique to muscle, is involved in the control of muscle protein synthesis. Creatine is shown to stimulate selectively the rate of synthesis of two major contractile proteins, actin and myosin heavy chain, in cultures of differentiating skeletal muscle. Creatine affects only the rate of synthesis and not the rate of degradation. Several creatine analogs are as effective as creatine in stimulating muscle protein synthesis, creatinine and amino acids such as arginine and glycine are not. Creatine stimulates myosin heavy chain synthesis twofold in cultures of embryonic muscle grown in either normal or dialyzed media.

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.

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.

scholarly journals Short-Term Oxandrolone Administration Stimulates Net Muscle Protein Synthesis in Young Men1

1999 ◽  
Vol 84 (8) ◽  
pp. 2705-2711 ◽  
Author(s):  
Melinda Sheffield-Moore ◽  
Randall J. Urban ◽  
Steven E. Wolf ◽  
J. Jiang ◽  
Don H. Catlin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Growth Factor ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Rt Pcr ◽  
Short Term ◽  
Healthy Men ◽  
Factor I

Short term administration of testosterone stimulates net protein synthesis in healthy men. We investigated whether oxandrolone[ Oxandrin (OX)], a synthetic analog of testosterone, would improve net muscle protein synthesis and transport of amino acids across the leg. Six healthy men [22 ± 1 (±se) yr] were studied in the postabsorptive state before and after 5 days of oral OX (15 mg/day). Muscle protein synthesis and breakdown were determined by a three-compartment model using stable isotopic data obtained from femoral arterio-venous sampling and muscle biopsy. The precursor-product method was used to determine muscle protein fractional synthetic rates. Fractional breakdown rates were also directly calculated. Total messenger ribonucleic acid (mRNA) concentrations of skeletal muscle insulin-like growth factor I and androgen receptor (AR) were determined using RT-PCR. Model-derived muscle protein synthesis increased from 53.5 ± 3 to 68.3 ± 5 (mean ± se) nmol/min·100 mL/leg (P &lt; 0.05), whereas protein breakdown was unchanged. Inward transport of amino acids remained unchanged with OX, whereas outward transport decreased (P &lt; 0.05). The fractional synthetic rate increased 44% (P &lt; 0.05) after OX administration, with no change in fractional breakdown rate. Therefore, the net balance between synthesis and breakdown became more positive with both methodologies (P &lt; 0.05) and was not different from zero. Further, RT-PCR showed that OX administration significantly increased mRNA concentrations of skeletal muscle AR without changing insulin-like growth factor I mRNA concentrations. We conclude that short term OX administration stimulated an increase in skeletal muscle protein synthesis and improved intracellular reutilization of amino acids. The mechanism for this stimulation may be related to an OX-induced increase in AR expression in skeletal muscle.

Modulation of muscle protein synthesis by insulin is maintained during neonatal endotoxemia

2006 ◽  
Vol 291 (1) ◽  
pp. E159-E166 ◽  
Author(s):  
Renan A. Orellana ◽  
Pamela M. J. O'Connor ◽  
Jill A. Bush ◽  
Agus Suryawan ◽  
M. Carole Thivierge ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Gastrocnemius Muscle ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Liver Protein ◽  
Fasting Insulin ◽  
Neonatal Pigs

Sepsis promotes insulin resistance and reduces protein synthesis in skeletal muscle of adults. The effect of sepsis on insulin-stimulated muscle protein synthesis has not been determined in neonates, a highly anabolic population that is uniquely sensitive to insulin. Overnight fasted neonatal pigs were infused for 8 h with endotoxin [lipopolysaccharide (LPS), 0 and 10 μg·kg−1·h−1]. Glucose and amino acids were maintained at fasting levels, insulin was clamped at either fasting or fed (2 or 10 μU/ml) levels, and fractional protein synthesis rates were determined at the end of the infusion. LPS infusion induced a septic-like state, as indicated by a sustained elevation in body temperature, heart rate, and cortisol. At fasting insulin levels, LPS reduced fractional protein synthesis rates in gastrocnemius muscle (−26%) but had no effect on the masseter and heart. By contrast, LPS stimulated liver protein synthesis (+28%). Increasing insulin to fed levels accelerated protein synthesis rates in gastrocnemius (controls by +38%, LPS by +60%), masseter (controls by +50%, LPS by +43%), heart (controls by +34%, LPS by +40%), and diaphragm (controls by +54%, LPS by +29%), and the response to insulin was similar in LPS and controls. Insulin did not alter protein synthesis in liver, kidney, or jejunum in either group. These findings suggest that acute endotoxemia lowers basal fasting muscle protein synthesis in neonates but does not alter the response of protein synthesis to insulin.

scholarly journals A reexamination of the effects of creatine on muscle protein synthesis in tissue culture.

1980 ◽  
Vol 84 (2) ◽  
pp. 294-297 ◽  
Author(s):  
D M Fry ◽  
M F Morales
Keyword(s):  
Protein Synthesis ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Total Protein ◽  
Competitive Inhibition ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Culture Dish ◽  
Wide Range ◽  
Total Creatine

Experiments designed to test the hypothesis that intracellular creatine level regulates the synthesis of muscle specific proteins have failed to demonstrate any creatine regulatory effect. Manipulation of the extracellular creatine in culture medium over a 5,700-fold range (1.3-7.4 mM) was successful in altering intracellular total creatine by only a factor of 20 (1.4-42 mg creatine/mg protein), an indication that muscle cells are able to regulate intracellular creatine levels over a wide range of external creatine concentrations. Alterations of cell creatine had no effect on either total protein synthesis or synthesis of myosin heavy chain. Methods were perfected to measure total creatine, and incorporation of [3H]leucine into total protein and purified myosin heavy chain from the same culture dish to avoid the possibility of variation between dishes. The creatine analog 1-carboxymethyl-2-iminohexahydropyrimidine (CMIP) previously reported to stimulate myosin synthesis in culture was found to depress creatine accumulation by cells and depressed total protein synthesis and synthesis of myosin heavy chain. This inhibitory action of CMIP is consistent with the reported competitive inhibition of creatine kinase and presumed interference with energy metabolism.

scholarly journals The impact of delivery profile of essential amino acids upon skeletal muscle protein synthesis in older men: clinical efficacy of pulse vs. bolus supply

2015 ◽  
Vol 309 (5) ◽  
pp. E450-E457 ◽  
Author(s):  
W. Kyle Mitchell ◽  
Bethan E. Phillips ◽  
John P. Williams ◽  
Debbie Rankin ◽  
Jonathan N. Lund ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Blood Flow ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Older Men ◽  
Essential Amino Acids ◽  
Low Amplitude ◽  
The Impact

Essential amino acids (EAA) are responsible for skeletal muscle anabolic effects after nutrient intake. The pattern of appearance of EAA in blood, e.g., after intake of “slow” or “fast” protein sources or in response to grazing vs. bolus feeding patterns, may impact anabolism. However, the influence of this on muscle anabolism is poorly understood, particularly in older individuals. We determined the effects of divergent feeding profiles of EAA on blood flow, anabolic signaling, and muscle protein synthesis (MPS) in older men. Sixteen men (∼70 yr) consumed EAA either as a single dose (bolus, 15 g; n = 8) or as small repeated fractions (pulse, 4 × 3.75 g every 45 min; n = 8) during 13C6 phenylalanine infusion. Repeated blood samples and muscle biopsies permitted measurement of fasting and postprandial plasma EAA, insulin, anabolic signaling, and MPS. Muscle blood flow was assessed by contrast-enhanced ultrasound (Sonovue). Bolus achieved rapid insulinemia (12.7 μiU/ml 25-min postfeed), essential aminoacidemia (∼3,000 μM, 45–65 min postfeed), and mTORC1 activity; pulse achieved attenuated insulin responses, gradual low-amplitude aminoacidemia (∼1,800 μM 80–195 min after feeding), and undetectable mTORC1 signaling. Despite this, equivalent anabolic responses were observed: fasting FSRs of 0.051 and 0.047%/h (bolus and pulse, respectively) increased to 0.084 and 0.073%/h, respectively. Moreover, pulse led to sustainment of MPS beyond 180 min, when bolus MPS had returned to basal rates. We detected no benefit of rapid aminoacidemia in this older population despite enhanced anabolic signaling and greater overall EAA exposure. Rather, apparent delayed onset of the “muscle-full” effect permitted identical MPS following low-amplitude-sustained EAA exposure.

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