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Division of Nutritional Sciences and the Department of Food Science and Human Nutrition, University of Illinois, Urbana, IL 61801
3To whom correspondence should be addressed.
 |
ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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KEY WORDS: • leucine • protein synthesis • glycogen • exercise • rats
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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) and inhibition of skeletal
muscle protein synthesis (Davis and Karl 1986
,
Dohm et al. 1980
). Strategies to achieve recovery after
strenuous exercise have focused on repletion of carbohydrates with
little attention directed towards protein or amino acids. Further,
potential synergistic effects of carbohydrate and amino acids have not
been explored.
Consumption of carbohydrate following exercise results in rapid
increases in the rate of muscle glycogen synthesis and recovery of
muscle glycogen stores (Blom et al. 1987
, Ivy et
al. 1988
). These responses to carbohydrate intake are believed
to require increased plasma insulin. Elevated insulin levels increase
the rate of skeletal muscle glucose transport, providing adequate
substrate for glycogen synthesis. Additionally, insulin activates
glycogen synthase, the rate-limiting enzyme in glycogen synthesis
(Ivy 1991
, James et al. 1985
).
Whereas glucose is the primary stimulant for insulin secretion, certain
amino acids, such as leucine, arginine, and methionine are insulin
secretagogues (Malaisse 1984
). Furthermore, intravenous
infusion of glucose in combination with leucine or arginine has a
synergistic effect on insulin secretion in humans (Floyd et al. 1967
). These studies suggest that carbohydrate in combination
with certain amino acids could enhance muscle glycogen recovery by
further stimulating insulin secretion.
Postexercise nutrition also plays an important role in the stimulation
of protein synthesis following exercise. We recently demonstrated that
postexercise food intake improves recovery and that meal composition
affects the rate of recovery (Gautsch et al. 1998
). Rats
administered a purely carbohydrate meal by oral gavage immediately
following 2-h treadmill running demonstrated no increase in muscle
protein synthesis 1 h after exercise compared to food-deprived
controls. Conversely, feeding a macronutrient-mixed meal increased
skeletal muscle protein synthesis rates by 30% to levels equivalent to
nonexercised controls. Plasma insulin concentrations of rats fed either
the carbohydrate meal or the mixed meal were similar; hence, the
enhanced rate of recovery cannot be attributed to a differential
insulin response. These data suggest that rapid recovery of protein
synthesis following exercise requires both elevated plasma insulin and
dietary protein or amino acids.
Previous studies suggest that the anabolic effect of dietary protein
may be attributable to specific amino acids. Garlick and Grant (1988)
reported that infusion of glucose plus branched-chain amino acids
(BCAA)4
stimulates protein synthesis in rats following 12-h food deprivation.
Further, several studies report that the branched-chain amino acid
leucine independently stimulates skeletal muscle protein synthesis
(Buse and Reid 1975
, Hong and Layman 1984
, Li and Jefferson 1978
). These data suggest
that leucine has a unique anabolic potential; however, prior studies
have not shown leucine to be effective in stimulating skeletal muscle
protein synthesis in vivo (Funabiki et al. 1992
,
McNurlan et al. 1982
). This result may be due to either
an insufficient dose of leucine or lack of stimulation of plasma
insulin concentrations.
The objective of this study was to determine the ability of leucine to enhance muscle recovery after exercise. Specifically, we examined the ability of leucine, alone or in combination with carbohydrate, to stimulate muscle glycogen restoration and skeletal muscle protein synthesis following a single bout of treadmill running in male rats.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The animal facilities and protocol were reviewed and approved by the Institutional Animal Care Review Board of the University of Illinois. Male Sprague-Dawley rats weighing 140–150 g were purchased from Harlan-Sprague Dawley, Indianapolis, IN. Upon arrival, rats were individually housed in wire-bottom cages in a room maintained at 23–25°C with a 12:12 h light-dark cycle. All animals had free access to tap water and a commercial pelleted diet (Harlan-Teklad Rodent Chow, Madison, WI) until the day of the experiment.
The day after arrival, all rats began an 8-d treadmill acclimation schedule that gradually increased in either speed or duration up to 30 m/min for 10 min. Rats that refused to run during the acclimation period were eliminated from the study. All exercise sessions began at the onset of the light period after the recording of body weight and were performed on a motor-driven treadmill set at a 1.5% grade.
Experimental design.
On the day of the experiment, all rats were deprived of food for 7 h and then randomly assigned to one of five treatment groups (n = 6 per group): SF, sedentary controls deprived of food for a total of 10 h (serving as the baseline); EF, exercised for 2 h and deprived of food for 1 h after the experimental run; EC, exercised and fed a 100% carbohydrate meal; EL, exercised and fed a 100% leucine meal; ECL, exercised and fed a combination of carbohydrate and leucine.
The carbohydrate meal provided 2.63 g of carbohydrate and
consisted of 262.5 g glucose/L and 262.5 g sucrose/L in distilled
water. The leucine meal provided 0.27 g of leucine prepared as
54.0 g leucine/L in distilled water and was equivalent to the
amount of leucine consumed by rats of this age and strain during
24 h of free access to AIN-93 powdered diet (Harlan-Teklad)
(Gautsch et al. 1998
). The carbohydrate plus leucine
meal was isocaloric with the carbohydrate meal and isonitrogenous with
the leucine meal (235.5 g glucose/L, 235.5 g sucrose/L, and 54.0 g
leucine/L in distilled water). The carbohydrate meal and the
carbohydrate plus leucine meal supplied ~15% of daily energy intake
for this age and strain of rat (Gautsch et al. 1998
).
The dosage for all experimental meals was 5 mL administered by oral
gavage immediately following the experimental run. SF and EF rats that
were not fed following exercise were administered 5 mL saline (0.155
mol NaCl/L). All rats were allowed free access to water following the
treadmill bout, but no food was available following exercise beyond
defined postexercise meals.
The experimental run consisted of 2 h of treadmill running at 36
m/min (1.5% grade). Exactly 1 h after the termination of the
experimental run, rats were anesthetized by a carbon dioxide overdose
and killed by decapitation. Trunk blood was collected in chilled
heparinized tubes and centrifuged at 1,800 x g for 10
min to obtain plasma. The decision to investigate muscle recovery
1 h after exercise was based on previous work in rodents, which
showed re-alimentation following food deprivation (Garlick et al. 1983
) or exercise (Gautsch et al. 1998
)
to increase muscle protein synthesis within 1 h after refeeding.
Administration of metabolic tracer.
A bolus dose (0.7 mL per 100 g body weight) of
L-[4,5-3H]-isoleucine (200 mmol/L, containing 4.81 GBq/L)
was injected via the tail vein 45 min after the end of exercise for the
measurement of skeletal muscle protein synthesis (Garlick et al. 1980
, Gautsch et al. 1998
). The right
gastrocnemius and plantaris were excised as a unit 15 min after
injection and quickly frozen in liquid nitrogen before storage in a
-80°C freezer. The elapsed time from injection until freezing was
recorded as the actual time for incorporation of the labeled amino acid
into protein.
Plasma measurements.
Plasma glucose was analyzed by a glucose oxidase-peroxidase automated method (YSI Model 2300 analyzer, Yellow Springs Instruments, Yellow Springs, OH). Plasma insulin was measured using a commercial RIA kit for rat insulin (Linco Research, St. Charles, MO).
Measurement of skeletal muscle glycogen.
Muscle glycogen was measured by a phenol-sulfuric acid colorimetric
assay as described by Lo et al. (1970)
. Briefly, frozen muscle was
powdered under liquid nitrogen with a mortar and pestle. A 50 mg sample
was weighed and combined with 0.5 mL 5.35 mol/L potassium hydroxide
saturated with sodium sulfate. Samples were boiled for 15 min until a
homogeneous solution was obtained, then cooled on ice for 30 min. To
precipitate glycogen, 0.6 mL of 95% ethanol was added, and samples
were chilled on ice for 30 min. Samples were centrifuged at 840 x
g for 25 min, and the supernatant was carefully
aspirated. The resulting pellets were resuspended in 3 mL of distilled
water. A standard curve ranging from 0 to 100 mg/L was prepared using a
glycogen stock solution [100 mg Bovine Liver Glycogen/L (Sigma, St.
Louis, MO) in distilled water]. Next, 1 mL of 50 g phenol/L was
added to a 1-mL aliquot of the resuspended muscle glycogen and to each
standard. Next 5 mL of 18.0 mol sulfuric acid/L was added to each tube,
and the samples were allowed to stand at room temperature for 10 min.
When samples had reached room temperature, they were vortexed, and the
absorbance was read at 490 nm.
Measurement of skeletal muscle protein synthesis.
Intracellular bound and free isoleucine was isolated from skeletal
muscle using the method described by Gautsch et al. (1998)
. Free and
protein-bound amino acid samples were derivatized with
phenylisothiocyanate (Paul et al. 1996
). The amount of
isoleucine in each was determined using HPLC (PICO-TAG method,
Millipore; Waters Chromatography, Milford, MA). The
radioactivity of isoleucine in free and protein-bound amino acid
samples was determined by liquid scintillation spectrometry (Model
LS9000 Liquid Scintillation Counter, Beckman Instruments, Palo Alto,
CA). Specific activity (SA) was calculated as described previously
(Paul et al. 1996
).
Calculation of the fractional rate of protein synthesis.
Protein synthesis was calculated as a fractional rate of synthesis
(Ks, %/d) according to McNurlan et al. (1979)
:
Ks = (Sinc x 100)/(Sfree x t) where
Sinc represents isoleucine SA incorporated into
muscle protein, Sfree represents the
intracellular free pool isoleucine SA, and t represents the infusion
time in days.
Statistics.
All data were analyzed by the STATISTICA® statistical software package for the Macintosh, volume II (StatSoft®, Tulsa, OK). A one-way ANOVA was performed to assess main effects with recovery group (exercise condition + meal) as the independent variable. When a significant overall effect was detected, differences among individual means were assessed with Duncan's Multiple Range post-hoc test. The level of significance was set at P < 0.05 for all statistical tests.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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) or insulin (Fig. 2
) below nonexercised controls (EF vs. SF) measured 1 h after
exercise. Feeding a carbohydrate meal (EC) resulted in plasma glucose
and insulin concentrations that were two- and threefold greater than in
EF rats, respectively. In contrast, rats fed only leucine (EL) did not
differ from EF rats in plasma glucose or insulin. Feeding a combination
of carbohydrate and leucine (ECL) resulted in a fivefold stimulation of
plasma insulin, but plasma glucose was not significantly different than
the EF group. The ECL group had plasma glucose levels that were
significantly greater than those of EL rats.
|
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). Recovery of glycogen was enhanced by postexercise feeding and
the degree of glycogen restoration correlated with plasma insulin
concentrations (r = 0.58, P < 0.05).
Refeeding carbohydrate (EC) or carbohydrate plus leucine (ECL)
stimulated recovery of skeletal muscle glycogen 1 h after
exercise, with values 76 and 88% of nonexercised controls,
respectively. In contrast, rats administered leucine alone (EL) did not
demonstrate significant improvement in glycogen concentration relative
to EF rats.
|
). Feeding carbohydrate alone (EC) did not promote recovery of
muscle protein synthesis. In contrast, supplements containing the
branched-chain amino acid leucine (EL and ECL) reversed the
depression in protein synthesis, resulting in protein synthesis values
that were not different from nonexercised controls (SF) 1 h after
exercise.
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|
DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Efficient restoration of muscle glycogen following exercise is a key
component to muscle recovery. Numerous studies have established that
adequate carbohydrate intake following exercise is essential to promote
muscle glycogen recovery (reviewed by Ivy, 1991
). Although the direct
effect of carbohydrate intake on skeletal muscle glycogen after
exercise is well documented, few studies have explored the effects of
meal composition on glycogen restoration following prolonged exercise.
Zawadzki et al. (1992)
reported that a combination of carbohydrate and
protein improves the rate of glycogen synthesis over either nutrient
alone in men recovering after exercise. These results were attributed
to an increased plasma insulin response; however, the study was not
designed to control for total energy intake. The combination
carbohydrate and protein supplement was an additive mixture of the
carbohydrate supplement plus the protein supplement. In contrast,
Tarnopolsky et al. (1997)
examined the effects of isoenergetic
supplements of carbohydrate and protein verses carbohydrate alone on
skeletal muscle glycogen recovery following prolonged exercise.
Although both supplements resulted in increased muscle glycogen
compared to placebo after exercise, the combination of carbohydrate and
protein did not stimulate glycogen resynthesis beyond carbohydrate
alone. Thus, the efficacy of amino acid supplementation for glycogen
repletion remains equivocal.
In the present study, rats administered carbohydrate plus leucine demonstrated greater plasma insulin (+34%) and muscle glycogen (+14%) values compared to those administered carbohydrate alone. These differences were observed despite 10% less total carbohydrate in the combination meal. These results suggest that the rate of recovery of muscle glycogen stores appears to be determined to a greater extent by the magnitude of the plasma insulin response than by the absolute amount of carbohydrate in the postexercise meal. This conclusion is supported by our observation that a significant positive correlation (r = 0.58, P < 0.05) existed between plasma insulin and muscle glycogen concentrations in exercised animals.
Prolonged exercise also induces acute catabolic changes in protein
synthesis (Dohm et al. 1980
); however, exercise is
associated with maintenance or hypertrophy of skeletal muscle and not
atrophy (Davis and Karl 1986
). Clearly at some point
during recovery, rates of protein synthesis must increase. This
suggests that efficient recovery of protein synthesis is essential to
drive the anabolic processes associated with regular exercise programs
and maintenance or development of muscle mass.
Postexercise meal composition can have a profound effect on muscle
recovery. We recently reported that a macronutrient-mixed meal
administered immediately following exercise enhances the rate of
skeletal muscle protein synthesis during recovery (Gautsch et al. 1998
). In contrast, feeding carbohydrate alone did not
stimulate protein synthesis rates above those of rats food deprived
after exercise. Plasma insulin levels were elevated to a similar degree
in rats fed either the macronutrient-mixed meal or the carbohydrate
meal, suggesting that insulin acts in concert with some other component
of the mixed meal to stimulate protein synthesis.
Other investigators hypothesize that insulin and amino acids act in
concert to stimulate protein synthesis (Preedy and Garlick 1986
, Yoshizawa et al. 1995
). Preedy and Garlick (1986)
reported that infusion of glucose and amino acids stimulated
protein synthesis in rats following 12 h food deprivation.
Conversely, infusion of amino acids and glucose plus insulin antiserum
did not stimulate muscle protein synthesis rates despite a significant
rise in plasma glucose concentrations. Similarly, Yoshizawa et al. (1995)
reported that refeeding mice a nutritionally complete meal, but
not a protein-free meal, stimulated muscle protein synthesis
following overnight food deprivation. These experiments suggest that
amino acids and insulin act together to stimulate protein synthesis
following a fast.
A study by Biolo et al. (1997)
also suggests that the anabolic effect
of amino acids on protein synthesis following exercise is also
concomitant with elevations in plasma insulin. The authors reported
that amino acids enhance the rate of skeletal muscle protein synthesis
during exercise recovery. Normal male subjects were studied during a
3-h intravenous infusion of a complete amino acid mixture at rest or
following a bout of leg resistance exercise. Muscle protein synthesis
was significantly increased after exercise when amino acids were
provided. The amino acid infusion produced elevated levels of plasma
amino acids and insulin and increased levels of amino acid transport
into muscle. These data suggest that amino acids ingested after
exercise may promote rapid increases in skeletal muscle protein
synthesis.
Previously, the effects of oral administration of specific amino acids on recovery of protein synthesis after exercise have not been studied. This is the first report that an oral dose of leucine enhances protein synthesis following exercise. Furthermore, leucine independently stimulated protein synthesis almost as effectively as a combination of carbohydrate and leucine, despite plasma insulin concentrations that were not statistically different than sedentary or exercised controls. These results indicate that leucine is capable of stimulating recovery of muscle protein synthesis after exhaustive exercise and that this effect is not dependent on elevated levels of plasma insulin.
While this study demonstrates that increased rates of skeletal muscle
protein synthesis are independent of changes in plasma insulin
concentration, these results do not address the role of basal levels of
insulin in modulating protein synthesis in these rats. Prior studies
demonstrate that either exercise (Davis and Karl 1986
)
or BCAA (Garlick and Grant 1988
) may independently
increase the sensitivity of skeletal muscle protein synthesis to
insulin. Therefore, the combination of leucine with exercise may
stimulate protein synthesis by enhancing muscle sensitivity to
available insulin.
The inability of other investigators to demonstrate that leucine
independently stimulates skeletal muscle protein synthesis in vivo may
be attributable to an insufficient quantity of leucine administered to
the animal. Previously, investigators used leucine doses in the range
of 100–360 µmol/100 g body weight (Funabiki et al. 1992
, McNurlan et al. 1982
). In the
present study, both the leucine meal and the combination of leucine
plus carbohydrate contained ~1,030 µmol/100 g body weight. This
amount is equivalent to the amount of leucine this age and strain of
rat consumes over 24 h with free access to AIN-93 powdered diet
(Harlan-Teklad) (Gautsch et al. 1998
). This dose was
chosen to maximize effects of leucine. Taken together, these findings
suggest that leucine stimulation of skeletal muscle protein synthesis
is dose dependent.
The mechanism for stimulation of muscle protein synthesis by leucine
remains unclear. Buse and Reid (1975)
suggest that leucine exerts its
effects at a posttranscriptional level and most likely during
initiation. This conclusion is based on in vitro data demonstrating
that pretreatment of rat diaphragms with actinomycin D does not inhibit
the stimulatory effects of leucine on protein synthesis. This is
further supported by Li and Jefferson (1978)
who reported that the
stimulatory effect of leucine on protein synthesis in perfused rats is
associated with a decrease in the level of free ribosomal subunits.
Recently, Kimball et al. (1998)
demonstrated that leucine stimulates
the activity and increases the availability of specific proteins
required for translation initiation in L6 myoblasts. Further, we found
that rates of protein synthesis following exercise are capable of rapid
changes and that these alterations are associated with changes in
translation initiation factors (Gautsch et al. 1998
).
Specifically, we demonstrated that recovery of muscle protein synthesis
after exercise correlates to the availability of eukaryotic initiation
factor 4E (eIF4E) for 48S pre-initiation ribosomal complex
formation. Moreover, recent papers by Hara et al. (1998)
and Xu et al. (1998)
report that amino acids, and specifically leucine, have a direct
action on the phosphatidylinositol 3-kinase signal pathway in
activating the eIF4E initiation complex and that this effect is
independent of insulin (Patti et al. 1998
). The
physiological impact of leucine on this signal pathway remains to be
further elucidated.
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FOOTNOTES |
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2 Supported by research grant HD-27558 from the
National Institutes of Health.
4 Abbreviations used: BCAA, branched chain amino
acids; EC, exercised and fed a 100% carbohydrate meal; ECL, exercised
and fed a combination of carbohydrate and leucine; EF, exercised and
food deprived; eIF4E, eukaryotic initiation factor 4E; EL, exercised
and fed leucine; Ks, fractional rate of skeletal muscle
protein synthesis; SA, specific activity; SF, sedentary and food
deprived; Sfree, intracellular free pool isoleucine
specific activity; Sinc, isoleucine specific activity
incorporated into muscle protein; t, infusion time in days.
Manuscript received September 7, 1998. Initial review completed November 6, 1998. Revision accepted March 5, 1999.
|
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P. J. Garlick The Role of Leucine in the Regulation of Protein Metabolism J. Nutr., June 1, 2005; 135(6): 1553S - 1556S. [Abstract] [Full Text] [PDF]
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R. Koopman, A. J. M. Wagenmakers, R. J. F. Manders, A. H. G. Zorenc, J. M. G. Senden, M. Gorselink, H. A. Keizer, and L. J. C. van Loon Combined ingestion of protein and free leucine with carbohydrate increases postexercise muscle protein synthesis in vivo in male subjects Am J Physiol Endocrinol Metab, April 1, 2005; 288(4): E645 - E653. [Abstract] [Full Text] [PDF]
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S. J. Crozier, S. R. Kimball, S. W. Emmert, J. C. Anthony, and L. S. Jefferson Oral Leucine Administration Stimulates Protein Synthesis in Rat Skeletal Muscle J. Nutr., March 1, 2005; 135(3): 376 - 382. [Abstract] [Full Text] [PDF]
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C. H. Lang and R. A. Frost Differential effect of sepsis on ability of leucine and IGF-I to stimulate muscle translation initiation Am J Physiol Endocrinol Metab, October 1, 2004; 287(4): E721 - E730. [Abstract] [Full Text] [PDF]
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C. H. Lang, R. A. Frost, N. Deshpande, V. Kumar, T. C. Vary, L. S. Jefferson, and S. R. Kimball Alcohol impairs leucine-mediated phosphorylation of 4E-BP1, S6K1, eIF4G, and mTOR in skeletal muscle Am J Physiol Endocrinol Metab, December 1, 2003; 285(6): E1205 - E1215. [Abstract] [Full Text] [PDF]
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D. K. Layman, R. A. Boileau, D. J. Erickson, J. E. Painter, H. Shiue, C. Sather, and D. D. Christou A Reduced Ratio of Dietary Carbohydrate to Protein Improves Body Composition and Blood Lipid Profiles during Weight Loss in Adult Women J. Nutr., February 1, 2003; 133(2): 411 - 417. [Abstract] [Full Text] [PDF]
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D. K. Layman The Role of Leucine in Weight Loss Diets and Glucose Homeostasis J. Nutr., January 1, 2003; 133(1): 261S - 267. [Abstract] [Full Text] [PDF]
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 Z. Liu, L. A. Jahn, L. Wei, W. Long, and E. J. Barrett Amino Acids Stimulate Translation Initiation and Protein Synthesis through an Akt-Independent Pathway in Human Skeletal Muscle J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5553 - 5558. [Abstract] [Full Text] [PDF]
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 A. J. Kee, A. J. Taylor, A. R. Carlsson, A. Sevette, R. C. Smith, and M. W. Thompson IGF-I has no effect on postexercise suppression of the ubiquitin-proteasome system in rat skeletal muscle J Appl Physiol, June 1, 2002; 92(6): 2277 - 2284. [Abstract] [Full Text] [PDF]
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J. C. Anthony, C. H. Lang, S. J. Crozier, T. G. Anthony, D. A. MacLean, S. R. Kimball, and L. S. Jefferson Contribution of insulin to the translational control of protein synthesis in skeletal muscle by leucine Am J Physiol Endocrinol Metab, May 1, 2002; 282(5): E1092 - E1101. [Abstract] [Full Text] [PDF]
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J. C. Anthony, A. K. Reiter, T. G. Anthony, S. J. Crozier, C. H. Lang, D. A. MacLean, S. R. Kimball, and L. S. Jefferson Orally Administered Leucine Enhances Protein Synthesis in Skeletal Muscle of Diabetic Rats in the Absence of Increases in 4E-BP1 or S6K1 Phosphorylation Diabetes, April 1, 2002; 51(4): 928 - 936. [Abstract] [Full Text] [PDF]
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D. Dardevet, C. Sornet, G. Bayle, J. Prugnaud, C. Pouyet, and J. Grizard Postprandial Stimulation of Muscle Protein Synthesis in Old Rats Can Be Restored by a Leucine-Supplemented Meal J. Nutr., January 1, 2002; 132(1): 95 - 100. [Abstract] [Full Text] [PDF]
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E. Blomstrand and B. Saltin BCAA intake affects protein metabolism in muscle after but not during exercise in humans Am J Physiol Endocrinol Metab, August 1, 2001; 281(2): E365 - E374. [Abstract] [Full Text] [PDF]
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Z. Liu, L. A. Jahn, W. Long, D. A. Fryburg, L. Wei, and E. J. Barrett Branched Chain Amino Acids Activate Messenger Ribonucleic Acid Translation Regulatory Proteins in Human Skeletal Muscle, and Glucocorticoids Blunt This Action J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2136 - 2143. [Abstract] [Full Text]
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T. G. Anthony, J. C. Anthony, F. Yoshizawa, S. R. Kimball, and L. S. Jefferson Oral Administration of Leucine Stimulates Ribosomal Protein mRNA Translation but Not Global Rates of Protein Synthesis in the Liver of Rats J. Nutr., April 1, 2001; 131(4): 1171 - 1176. [Abstract] [Full Text]
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J. C. Anthony, T. G. Anthony, S. R. Kimball, and L. S. Jefferson Signaling Pathways Involved in Translational Control of Protein Synthesis in Skeletal Muscle by Leucine J. Nutr., March 1, 2001; 131(3): 856S - 860. [Abstract] [Full Text]
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O. J. Shah, J. C. Anthony, S. R. Kimball, and L. S. Jefferson Glucocorticoids oppose translational control by leucine in skeletal muscle Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E1185 - E1190. [Abstract] [Full Text] [PDF]
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J. C. Anthony, F. Yoshizawa, T. G. Anthony, T. C. Vary, L. S. Jefferson, and S. R. Kimball Leucine Stimulates Translation Initiation in Skeletal Muscle of Postabsorptive Rats via a Rapamycin-Sensitive Pathway J. Nutr., October 1, 2000; 130(10): 2413 - 2419. [Abstract] [Full Text]
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L. J. C. van Loon, M. Kruijshoop, H. Verhagen, W. H. M. Saris, and A. J. M. Wagenmakers Ingestion of Protein Hydrolysate and Amino Acid-Carbohydrate Mixtures Increases Postexercise Plasma Insulin Responses in Men J. Nutr., October 1, 2000; 130(10): 2508 - 2513. [Abstract] [Full Text]
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J. C. Anthony, T. G. Anthony, S. R. Kimball, T. C. Vary, and L. S. Jefferson Orally Administered Leucine Stimulates Protein Synthesis in Skeletal Muscle of Postabsorptive Rats in Association with Increased eIF4F Formation J. Nutr., January 1, 2000; 130(2): 139 - 145. [Abstract] [Full Text]
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