scholarly journals Glucocorticoid effects on insulin- and IGF-I-regulated muscle protein metabolism during aging

1998 ◽  
Vol 156 (1) ◽  
pp. 83-89 ◽  
Author(s):  
D Dardevet ◽  
C Sornet ◽  
I Savary ◽  
E Debras ◽  
P Patureau-Mirand ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Atrophy ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Recovery Period ◽  
Adult Rats ◽  
Igf I ◽  
Muscle Protein Metabolism ◽  
Old Rats

This study was performed to assess the effect of glucocorticoids (dexamethasone) on insulin- and IGF-I-regulated muscle protein metabolism in adult and old rats. Muscle atrophy occurred more rapidly in old rats, and recovery of muscle mass was impaired when compared with adults. Muscle wasting resulted mainly from increased protein breakdown in adult rat but from depressed protein synthesis in the aged animal. Glucocorticoid treatment significantly decreased the stimulatory effect of insulin and IGF-I on muscle protein synthesis in adult rats by 25.9 and 58.1% respectively. In old rats, this effect was even greater, being 49.3 and 100% respectively. With regard to muscle proteolysis, glucocorticoids blunted the anti-proteolytic action of insulin and IGF-I in both age groups. During the recovery period, adult rats reversed the glucocorticoid-induced resistance of muscle protein metabolism within 3 days, at which time old rats still exhibited the decrease in insulin-regulated proteolysis. In conclusion, the higher sensitivity of old rat muscle to glucocorticoids may in part result from the greater modification of the effects of insulin and IGF-I on muscle protein metabolism. These responses to glucocorticoids in old rats may be associated with the emergence of muscle atrophy with advancing age.

Age and aerobic exercise training effects on whole body and muscle protein metabolism

2004 ◽  
Vol 286 (1) ◽  
pp. E92-E101 ◽  
Author(s):  
Kevin R. Short ◽  
Janet L. Vittone ◽  
Maureen L. Bigelow ◽  
David N. Proctor ◽  
K. Sreekumaran Nair
Keyword(s):  
Protein Synthesis ◽  
Exercise Training ◽  
Protein Metabolism ◽  
Protein Turnover ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Fat Free Mass ◽  
Whole Body ◽  
Men And Women ◽  
Muscle Protein Metabolism

Aging in humans is associated with loss of lean body mass, but the causes are incompletely defined. Lean tissue mass and function depend on continuous rebuilding of proteins. We tested the hypotheses that whole body and mixed muscle protein metabolism declines with age in men and women and that aerobic exercise training would partly reverse this decline. Seventy-eight healthy, previously untrained men and women aged 19-87 yr were studied before and after 4 mo of bicycle training (up to 45 min at 80% peak heart rate, 3-4 days/wk) or control (flexibility) activity. At the whole body level, protein breakdown (measured as [13C]leucine and [15N]phenylalanine flux), Leu oxidation, and protein synthesis (nonoxidative Leu disposal) declined with age at a rate of 4-5% per decade ( P < 0.001). Fat-free mass was closely correlated with protein turnover and declined 3% per decade ( P < 0.001), but even after covariate adjustment for fat-free mass, the decline in protein turnover with age remained significant. There were no differences between men and women after adjustment for fat-free mass. Mixed muscle protein synthesis also declined with age 3.5% per decade ( P < 0.05). Exercise training improved aerobic capacity 9% overall ( P < 0.01), and mixed muscle protein synthesis increased 22% ( P < 0.05), with no effect of age on the training response for either variable. Fat-free mass, whole body protein turnover, and resting metabolic rate were unchanged by training. We conclude that rates of whole body and muscle protein metabolism decline with age in men and women, thus indicating that there is a progressive decline in the body's remodeling processes with aging. This study also demonstrates that aerobic exercise can enhance muscle protein synthesis irrespective of age.

Muscle protein metabolism in female swimmers after a combination of resistance and endurance exercise

1996 ◽  
Vol 81 (5) ◽  
pp. 2034-2038 ◽  
Author(s):  
Kevin D. Tipton ◽  
Arny A. Ferrando ◽  
Bradley D. Williams ◽  
Robert R. Wolfe
Keyword(s):  
Protein Synthesis ◽  
Resistance Training ◽  
Endurance Exercise ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Whole Body ◽  
Protein Breakdown ◽  
Body Protein ◽  
Muscle Protein Metabolism

Tipton, Kevin D., Arny A. Ferrando, Bradley D. Williams, and Robert R. Wolfe. Muscle protein metabolism in female swimmers after a combination of resistance and endurance exercise. J. Appl. Physiol. 81(5): 2034–2038, 1996.—There is little known about the responses of muscle protein metabolism in women to exercise. Furthermore, the effect of adding resistance training to an endurance training regimen on net protein anabolism has not been established in either men or women. The purpose of this study was to quantify the acute effects of combined swimming and resistance training on protein metabolism in female swimmers by the direct measurement of muscle protein synthesis and whole body protein degradation. Seven collegiate female swimmers were each studied on four separate occasions with a primed constant infusion of ring-[13C6]phenylalanine (Phe) to measure the fractional synthetic rate (FSR) of the posterior deltoid and whole body protein breakdown. Measurements were made over a 5-h period at rest and after each of three randomly ordered workouts: 1) 4,600 m of intense interval swimming (SW); 2) a whole body resistance-training workout with no swimming on that day (RW); and 3) swimming and resistance training combined (SR). Whole body protein breakdown was similar for all treatments (0.75 ± 0.04, 0.69 ± 0.03, 0.69 ± 0.02, and 0.71 ± 0.04 μmol ⋅ min−1 ⋅ kg−1for rest, RW, SW, and SR, respectively). The FSR of the posterior deltoid was significantly greater ( P< 0.05) after SR (0.082 ± 0.015%/h) than at rest (0.045 ± 0.006%/h). There was no significant difference in the FSR after RW (0.048 ± 0.004%/h) or SW (0.064 ± 0.008%/h) from rest or from SR. These data indicate that the combination of swimming and resistance exercise stimulates net muscle protein synthesis above resting levels in female swimmers.

Anabolic resistance: the effects of aging, sexual dimorphism, and immobilization on human muscle protein turnoverThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

2009 ◽  
Vol 34 (3) ◽  
pp. 377-381 ◽  
Author(s):  
Michael J. Rennie
Keyword(s):  
Protein Synthesis ◽  
Protein Metabolism ◽  
Older Persons ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Anabolic Resistance ◽  
Muscle Protein Metabolism ◽  
The Right

In healthy active older persons, there is no derangement of muscle protein metabolism. However, there is a major deficit in the ability of older muscles to regulate their maintenance during feeding and exercise. The dose–response relationship between myofibrillar protein synthesis and the availability of essential amino acids (EAA) is shifted down and to the right, and giving extra amino acids is unable to overcome this. There is no sex difference in basal or fed muscle protein metabolism in the young, but postmenopausal women have a greater anabolic resistance than older men. Anabolic resistance is also shown by the decreased phosphorylation in the PKB–mTOR–eIF4BP1 pathway in response to increased EAA. The muscle synthetic system is refractory to EAA provision, irrespective of the availability of insulin, insulin-like growth factor 1, and growth hormone. However, insulin is a major regulator of muscle protein breakdown, and there is a blunting of the ability of older muscle to decrease proteolysis in response to low concentrations of insulin, such as those observed after a light breakfast. Providing more EAA seems not to be useful, and modern N-balance data confirm that the dietary protein requirements of older persons are not increased. The sigmoidal dose–response relationship between muscle protein synthesis and resistance exercise intensity is shifted downward and to the right in older men. Decreased physical activity itself, even in young subjects, can produce anabolic resistance of muscle protein synthesis, which cannot be overcome by increasing amino acid availability. Exercise may retune the amino acid and (or) insulin sensitivity of muscle in older people.

Epinephrine depletion exacerbates the fasting-induced protein breakdown in fast-twitch skeletal muscles

2013 ◽  
Vol 305 (12) ◽  
pp. E1483-E1494 ◽  
Author(s):  
Flávia A. Graça ◽  
Dawit A. P. Gonçalves ◽  
Wilian A. Silveira ◽  
Eduardo C. Lira ◽  
Valéria Ernestânia Chaves ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Metabolism ◽  
Skeletal Muscles ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Physiological Role ◽  
Protein Breakdown ◽  
Muscle Protein Metabolism ◽  
Fast Twitch ◽  
Fasted Rats

The physiological role of epinephrine in the regulation of skeletal muscle protein metabolism under fasting is unknown. We examined the effects of plasma epinephrine depletion, induced by adrenodemedullation (ADMX), on muscle protein metabolism in fed and 2-day-fasted rats. In fed rats, ADMX for 10 days reduced muscle mass, the cross-sectional area of extensor digitorum longus (EDL) muscle fibers, and the phosphorylation levels of Akt. In addition, ADMX led to a compensatory increase in muscle sympathetic activity, as estimated by the rate of norepinephrine turnover; this increase was accompanied by high rates of muscle protein synthesis. In fasted rats, ADMX exacerbated fasting-induced proteolysis in EDL but did not affect the low rates of protein synthesis. Accordingly, ADMX activated lysosomal proteolysis and further increased the activity of the ubiquitin (Ub)-proteasome system (UPS). Moreover, expression of the atrophy-related Ub ligases atrogin-1 and MuRF1 and the autophagy-related genes LC3b and GABARAPl1 were upregulated in EDL muscles from ADMX-fasted rats compared with sham-fasted rats, and ADMX reduced cAMP levels and increased fasting-induced Akt dephosphorylation. Unlike that observed for EDL muscles, soleus muscle proteolysis and Akt phosphorylation levels were not affected by ADMX. In isolated EDL, epinephrine reduced the basal UPS activity and suppressed overall proteolysis and atrogin-1 and MuRF1 induction following fasting. These data suggest that epinephrine released from the adrenal medulla inhibits fasting-induced protein breakdown in fast-twitch skeletal muscles, and these antiproteolytic effects on the UPS and lysosomal system are apparently mediated through a cAMP-Akt-dependent pathway, which suppresses ubiquitination and autophagy.

scholarly journals Phenotypic regulation of animal skeletal muscle protein metabolism

2019 ◽  
Vol 9 (4) ◽  
pp. 651-656 ◽  
Author(s):  
K. T. Erimbetov ◽  
O. V. Obvintseva ◽  
A. V. Fedorova ◽  
R. A. Zemlyanoy ◽  
A. G. Solovieva
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Signaling Pathways ◽  
Muscle Mass ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mrna Translation ◽  
Mtorc1 Signaling ◽  
Muscle Protein Metabolism

This review highlights the current state of phenotypic mechanisms of regulation of muscle protein metabolism in animals. Since the skeletal muscle represents 40–50% of body mass in mammals it is a critical regulator of overall metabolism. Therefore, an understanding of the processes involved in the postnatal increase in muscle mass, with associated accumulation of protein, is fundamental. Throughout life, a delicate balance exists between protein synthesis and degradation that is essential for growth and normal health of humans and animals. Signaling pathways coordinate muscle protein balance. Anabolic and catabolic stimuli are integrated through the PKB/Akt-mTORC1 signaling to regulate mechanisms that control muscle protein synthesis and breakdown. At an early periods of intensive growth, muscle mass is stimulated by an increase in protein synthesis at the level of mRNA translation. Throughout the life, proteolytic processes including autophagy lysosomal system, ubiquitin proteasome pathway, calcium-dependent calpains and cysteine protease caspase enzyme cascade influence the growth of muscle mass. Several signal transmission networks direct and coordinate these processes along with quality control mechanisms to maintain protein homeostasis (proteostasis). Genetic factors, hormones, amino acids, phytoecdysteroids, and rhodanines affect the protein metabolism via signaling pathways, changing the ability and / or efficiency of muscle growth.

scholarly journals Exercise, Protein Metabolism, and Muscle Growth

2001 ◽  
Vol 11 (1) ◽  
pp. 109-132 ◽  
Author(s):  
Kevin D. Tipton ◽  
Robert R. Wolfe
Keyword(s):  
Protein Synthesis ◽  
Protein Metabolism ◽  
Muscle Hypertrophy ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Growth ◽  
Protein Breakdown ◽  
Muscle Protein Breakdown ◽  
Amino Acid Availability ◽  
Muscle Protein Metabolism

Exercise has a profound effect on muscle growth, which can occur only if muscle protein synthesis exceeds muscle protein breakdown; there must be a positive muscle protein balance. Resistance exercise improves muscle protein balance, but, in the absence of food intake, the balance remains negative (i.e., catabolic). The response of muscle protein metabolism to a resistance exercise bout lasts for 24-48 hours; thus, the interaction between protein metabolism and any meals consumed in this period will determine the impact of the diet on muscle hypertrophy. Amino acid availability is an important regulator of muscle protein metabolism. The interaction of postexercise metabolic processes and increased amino acid availability maximizes the stimulation of muscle protein synthesis and results in even greater muscle anabolism than when dietary amino acids are not present. Hormones, especially insulin and testosterone, have important roles as regulators of muscle protein synthesis and muscle hypertrophy. Following exercise, insulin has only a permissive role on muscle protein synthesis, but it appears to inhibit the increase in muscle protein breakdown. Ingestion of only small amounts of amino acids, combined with carbohydrates, can transiently increase muscle protein anabolism, but it has yet to be determined if these transient responses translate into an appreciable increase in muscle mass over a prolonged training period.

Role of insulin and IGF-I in activation of muscle protein synthesis after oral feeding

1996 ◽  
Vol 270 (4) ◽  
pp. E614-E620 ◽  
Author(s):  
E. Svanberg ◽  
H. Zachrisson ◽  
C. Ohlsson ◽  
B. M. Iresjo ◽  
K. G. Lundholm
Keyword(s):  
Protein Synthesis ◽  
Skeletal Muscles ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Oral Feeding ◽  
Myofibrillar Proteins ◽  
Diabetic Mice ◽  
Igf I ◽  
Stimulation Of

The aim was to evaluate the role of insulin and insulin-like growth factor I (IGF-I) in activation of muscle protein synthesis after oral feeding. Synthesis rate of globular and myofibrillar proteins in muscle tissue was quantified by a flooding dose of radioactive phenylalanine. Muscle tissue expression of IGF-I mRNA was measured. Normal (C57 Bl) and diabetic mice (type I and type II) were subjected to an overnight fast (18 h) with subsequent refeeding procedures for 3 h with either oral chow intake or provision of insulin, IGF-I, glucose, and amino acids. Anti-insulin and anti-IGF-I were provided intraperitoneally before oral refeeding in some experiments. An overnight fast reduced synthesis of both globular (38 +/- 3%) and myofibrillar proteins (54 +/- 3%) in skeletal muscles, which was reversed by oral refeeding. Muscle protein synthesis, after starvation/ refeeding, was proportional and similar to changes in skeletal muscle IGF-I mRNA expression. Diabetic mice responded quantitatively similarly to starvation/refeeding in muscle protein synthesis compared with normal mice (C57 Bl). Both anti-insulin and anti-IGF-I attenuated significantly the stimulation of muscle protein synthesis in response to oral feeding, whereas exogenous provision of either insulin or IGF-I to overnight-starved and freely fed mice did not clearly stimulate protein synthesis in skeletal muscles. Our results support the suggestion that insulin and IGF-I either induce or facilitate the protein synthesis machinery in skeletal muscles rather than exerting a true stimulation of the biosynthetic process during feeding.

Adaptation to prolonged starvation in the rat: curtailment of skeletal muscle proteolysis

1981 ◽  
Vol 241 (4) ◽  
pp. E321-E327 ◽  
Author(s):  
M. N. Goodman ◽  
M. A. McElaney ◽  
N. B. Ruderman
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Early Event ◽  
Body Protein ◽  
Fed State ◽  
Prolonged Starvation ◽  
Obese Rats ◽  
Old Rats

Previous studies have established that 16-wk-old nonobese and obese rats conserve body protein during prolonged starvation. To determine the basis for this, protein synthesis and degradation in skeletal muscle were evaluated in the isolated perfused hindquarters of these rats, in the fed state and when starved for 2, 5, 10, and 11 days. Rats aged 4 and 8 wk were used as a comparison. The results indicate that the response to starvation depends on several factors: the age of the rat, its degree of adiposity, and the duration of the fast. An early event in starvation was a decline in muscle protein synthesis. This occurred in all groups, albeit this reduction occurred more slowly in the older rats. A later response to starvation was an increase in muscle proteolysis. This occurred between 2 and 5 days in the 8-wk-old rats. In 16-wk-old rats it did not occur until between 5 and 10 days, and it was preceded by a period of decreased proteolysis. In 16-wk-old obese rats, a decrease in proteolysis persisted for upwards of 10 days and the secondary increase was not noted during the period of study. The data suggest that the ability of older and more obese rats to conserve body protein during starvation is due, in part, to a curtailment of muscle proteolysis. This adaptation seems to correlate with the availability of lipid fuels.

Enhanced response of muscle protein synthesis and plasma insulin to food intake in suckled rats

1993 ◽  
Vol 265 (2) ◽  
pp. R334-R340 ◽  
Author(s):  
T. A. Davis ◽  
M. L. Fiorotto ◽  
H. V. Nguyen ◽  
P. J. Reeds
Keyword(s):  
Protein Synthesis ◽  
Food Intake ◽  
Plasma Insulin ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Fed State ◽  
Fasting And Refeeding ◽  
Old Rats ◽  
Amino Acid Concentrations

To compare the sensitivity of muscle protein synthesis to food intake in neonatal and weaned rats, 5- and 16-day-old suckled rats and 28-day-old weaned rats were either fed, fasted for 8-10 h, or refed for 1-4 h after an 8-h fast. Protein synthesis was measured in vivo in soleus and plantaris muscles with a large dose of L-[4-3H]phenylalanine. In fed rats, fractional rates of protein synthesis (KS) decreased with age. Fasting decreased KS, and refeeding increased KS most in 5-day-old animals, less in 16-day-old rats, and least in 28-day-old rats. In 5-day-old rats, there were no differences in KS between soleus and plantaris muscles in the fed state and after fasting and refeeding; at 28 days, KS was higher in soleus than in plantaris in fed rats, and the soleus did not respond to fasting and refeeding. In rats at all three ages, the concentration of most plasma amino acids decreased during fasting; when 5-day-old rats were refed, plasma amino acid concentrations increased, but not to the levels in the fed state. Plasma insulin concentrations increased with age. Plasma insulin concentrations decreased more rapidly with fasting and increased more extensively with refeeding in 5-day-old rats than in older rats. These results suggest that muscle protein synthesis is more responsive to food intake in young suckled rats than in older suckled or weaned rats; this increased responsiveness is accompanied by greater changes in circulating insulin concentrations.

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.

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