Muscle growth in response to mechanical stimuli

1995 ◽  
Vol 268 (2) ◽  
pp. E288-E297 ◽  
Author(s):  
D. F. Goldspink ◽  
V. M. Cox ◽  
S. K. Smith ◽  
L. A. Eaves ◽  
N. J. Osbaldeston ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Electrical Stimulation ◽  
Muscle Protein ◽  
Muscle Growth ◽  
Mrna Levels ◽  
Mechanical Stimuli ◽  
Static Stretch ◽  
Adaptive Growth ◽  
Igf I

The relative merits of the separate and combined uses of stretch and electrical stimulation at 10 Hz in influencing the rates of protein synthesis in vivo, proteolysis, and the growth of the extensor digitorum longus muscle have been investigated after 3 days in the rabbit. Continuous electrical stimulation failed to change muscle protein turnover or growth. Static stretch caused significant adaptive growth, with increases in c-fos, c-jun, and insulin-like growth factor I (IGF-I; 12-fold) mRNA levels, and protein (19%), RNA (128%), and DNA (45%) contents. Both the fractional (138%) and total (191%) rates of protein synthesis increased with stretch, correlating with increased ribosomal capacities. Combining stretch and electrical stimulation increased the mRNA concentration of IGF-I (40-fold). The adaptive growth was greater (35%), with massive increases in the nucleic acids (185 and 300%), ribosomal capacities (230%), and the rates of protein synthesis (345 and 450%). Large increases (i.e., 200-400%) in cathepsins B and L and dipeptidyl aminopeptidase I activities during stretch, with or without stimulation, suggest a role for these enzymes in tissue remodeling during muscle hypertrophy.

scholarly journals Proteasome- and Calpain-Mediated Proteolysis, but Not Autophagy, Is Required for Leucine-Induced Protein Synthesis in C2C12 Myotubes

Physiologia ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 22-33
Author(s):  
Shelby C. Osburn ◽  
Christopher G. Vann ◽  
David D. Church ◽  
Arny A. Ferrando ◽  
Michael D. Roberts
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Growth ◽  
Proteasome Inhibition ◽  
Coupled Processes ◽  
C2c12 Myotubes ◽  
Calpain Inhibitor ◽  
Tightly Coupled

Muscle protein synthesis and proteolysis are tightly coupled processes. Given that muscle growth is promoted by increases in net protein balance, it stands to reason that bolstering protein synthesis through amino acids while reducing or inhibiting proteolysis could be a synergistic strategy in enhancing anabolism. However, there is contradictory evidence suggesting that the proper functioning of proteolytic systems in muscle is required for homeostasis. To add clarity to this issue, we sought to determine if inhibiting different proteolytic systems in C2C12 myotubes in conjunction with acute and chronic leucine treatments affected markers of anabolism. In Experiment 1, myotubes underwent 1-h, 6-h, and 24-h treatments with serum and leucine-free DMEM containing the following compounds (n = 6 wells per treatment): (i) DMSO vehicle (CTL), (ii) 2 mM leucine + vehicle (Leu-only), (iii) 2 mM leucine + 40 μM MG132 (20S proteasome inhibitor) (Leu + MG132), (iv) 2 mM leucine + 50 μM calpeptin (calpain inhibitor) (Leu + CALP), and (v) 2 mM leucine + 1 μM 3-methyladenine (autophagy inhibitor) (Leu + 3MA). Protein synthesis levels significantly increased (p < 0.05) in the Leu-only and Leu + 3MA 6-h treatments compared to CTL, and levels were significantly lower in Leu + MG132 and Leu + CALP versus Leu-only and CTL. With 24-h treatments, total protein yield was significantly lower in Leu + MG132 cells versus other treatments. Additionally, the intracellular essential amino acid (EAA) pool was significantly greater in 24-h Leu + MG132 treatments versus other treatments. In a follow-up experiment, myotubes were treated for 48 h with CTL, Leu-only, and Leu + MG132 for morphological assessments. Results indicated Leu + MG132 yielded significantly smaller myotubes compared to CTL and Leu-only. Our data are limited in scope due to the utilization of select proteolysis inhibitors. However, this is the first evidence to suggest proteasome and calpain inhibition with MG132 and CALP, respectively, abrogate leucine-induced protein synthesis in myotubes. Additionally, longer-term Leu + MG132 treatments translated to an atrophy phenotype. Whether or not proteasome inhibition in vivo reduces leucine- or EAA-induced anabolism remains to be determined.

Influence of varying degrees of malnutrition on IGF-I expression in the rat diaphragm

2003 ◽  
Vol 95 (2) ◽  
pp. 555-562 ◽  
Author(s):  
Michael I. Lewis ◽  
Hongyan Li ◽  
Zhi-Shen Huang ◽  
Manmohan S. Biring ◽  
Bojan Cercek ◽  
...  
Keyword(s):  
Muscle Protein ◽  
Muscle Growth ◽  
The Body ◽  
Diaphragm Muscle ◽  
Fiber Types ◽  
Mrna Levels ◽  
Adult Rats ◽  
Cross Sectional ◽  
Igf I ◽  
The Impact

This study evaluated the impact of varying degrees of prolonged malnutrition on the local insulin-like growth factor-I (IGF-I) system in the costal diaphragm muscle. Adult rats were provided with either 60 or 40% of usual food intake over 3 wk. Nutritionally deprived (ND) animals (i.e., ND60 and ND40) were compared with control (Ctl) rats fed ad libitum. Costal diaphragm fiber types and cross-sectional areas were determined histochemically. Costal diaphragm muscle IGF-I mRNA levels were determined by RT-PCR. Serum and muscle IGF-I peptide levels were determined by using a rat-specific radioimmunoassay. The body weights of Ctl rats increased by 5%, whereas those of ND60 and ND40 animals decreased by 16 and 26%, respectively. Diaphragm weights were reduced by 17 and 27% in ND60 and ND40 animals, respectively, compared with Ctl. Diaphragm fiber proportions were unaffected by either ND regimen. Significant atrophy of both type IIa and IIx fibers was noted in the ND60 group, whereas atrophy of all three fiber types was observed in the diaphragm of ND40 rats. Serum IGF-I levels were reduced by 62 and 79% in ND60 and ND40 rats, respectively, compared with Ctl. Diaphragm muscle IGF-I mRNA levels in both ND groups were similar to those noted in Ctl. In contrast, IGF-I concentrations were reduced by 36 and 42% in the diaphragm muscle of ND60 and ND40 groups, respectively, compared with Ctl. We conclude that the local (autocrine/paracrine) muscle IGF-I system is affected in our models of prolonged ND. We propose that this contributes to disordered muscle protein turnover and muscle cachexia with atrophy of muscle fibers. This is particularly so in view of recent data demonstrating the importance of the autocrine/paracrine system in muscle growth and maintenance of fiber size.

IGF-I stimulation of muscle protein synthesis in the awake rat: permissive role of insulin and amino acids

1996 ◽  
Vol 270 (1) ◽  
pp. E60-E66 ◽  
Author(s):  
R. Jacob ◽  
X. Hu ◽  
D. Niederstock ◽  
S. Hasan ◽  
P. H. McNulty ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Plasma Insulin ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Amino Acid Replacement ◽  
Igf I ◽  
Awake Rat

Infusion of insulin-like growth factor I (IGF-I) lowers plasma amino acid and insulin concentrations, which may limit the capacity of IGF-I to promote muscle protein synthesis in vivo. We measured heart and skeletal muscle incorporation of continuously infused L-[ring-2,6-3H]phenylalanine in awake postabsorptive rats receiving 4-h intravenous infusions of saline (n = 11), IGF-I (1 microgram.kg-1.min-1) with (n = 10) or without (n = 11) amino acid replacement, or IGF-I with insulin replacement (n = 8). There were no significant increases in muscle protein synthesis during the infusion of IGF-I alone, which was associated with decreases in both plasma insulin (52 +/- 5%, P < 0.001) and amino acids (25 +/- 5%, P < 0.05). When IGF-I was given together with amino acids, protein synthesis was significantly increased in gastrocnemius (4.7 +/- 0.4 vs. 2.5 +/- 0.3%/day, P < 0.001), oblique (4.5 +/- 0.4 vs. 2.8 +/- 0.4%/day, P < 0.05), and soleus (8.8 +/- 0.7 vs. 6.4 +/- 0.3%/day, P < 0.01) and tended to be higher than saline control values in heart (10.9 +/- 0.9 vs. 8.8 +/- 0.7%/day, P = 0.08). Amino acid replacement prevented plasma concentrations from falling and also blunted the decline in plasma insulin (22 +/- 5%, P < 0.01 vs. IGF-I alone). When IGF-I and insulin replacement were given, protein synthesis was increased in heart (13.0 +/- 0.6%/day), gastrocnemius (4.7 +/- 0.4%/day), and oblique (4.5 +/- 0.4%/day) (P < 0.001 for each, compared with saline). We conclude that the action of IGF-I to acutely stimulate muscle protein synthesis in the awake rat is limited by the fall in circulating insulin and/or amino acid concentrations that accompanies IGF-I infusion in vivo and is prevented by co-infusion of insulin or amino acids.

scholarly journals Comparison of GH, IGF-I, and testosterone with mRNA of receptors and myostatin in skeletal muscle in older men

2001 ◽  
Vol 281 (6) ◽  
pp. E1159-E1164 ◽  
Author(s):  
Taylor J. Marcell ◽  
S. Mitchell Harman ◽  
Randall J. Urban ◽  
Daniel D. Metz ◽  
Buel D. Rodgers ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mrna Levels ◽  
Myostatin Gene ◽  
Healthy Older Adults ◽  
Skeletal Muscle Biopsy ◽  
Age Related ◽  
Igf I

Growth hormone (GH), insulin-like growth factor I (IGF-I), and testosterone (T) are important mediators of muscle protein synthesis, and thus muscle mass, all of which decline with age. We hypothesized that circulating hormones would be related to the transcriptional levels of their respective receptors and that this expression would be negatively related to expression of the myostatin gene. We therefore determined content of mRNA transcripts (by RT-PCR) for GH receptor (GHR), IGF-I, androgen receptor (AR), and myostatin in skeletal muscle biopsy samples from 27 healthy men >65 yr of age. There were no significant relationships between age, lean body mass, or percent body fat and transcript levels of GHR, IGF-I, AR, or myostatin. Moreover, there were no significant correlations of serum GH, IGF-I, or T with their corresponding target mRNA levels (GHR, intramuscular IGF-I, or AR) in skeletal muscle. However, GHR was negatively correlated ( r = −0.60, P = 0.001) with myostatin mRNA levels. The lack of apparent relationships of muscle transcripts with their respective ligands in healthy older adults suggests that age-related deficits in both GH and T may lead to an increase in myostatin expression and a disassociation in autocrine IGF-I effects on muscle protein synthesis, both of which could contribute to age-related sarcopenia.

Effects of dietary tryptophan on muscle growth, protein synthesis, and antioxidant capacity in hybrid catfish Pelteobagrus vachelli♀ × Leiocassis longirostris♂

2021 ◽  
pp. 1-35
Author(s):  
Qin Jiang ◽  
Ye Zhao ◽  
Xiao-Qiu Zhou ◽  
Xiao-Yun Wu ◽  
Shang-Xiao Xu ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Antioxidant Capacity ◽  
Protein Level ◽  
Muscle Protein ◽  
Mrna Level ◽  
Muscle Growth ◽  
Mrna Levels ◽  
Hybrid Catfish ◽  
Leiocassis Longirostris ◽  
Pelteobagrus Vachelli

Abstract The present study evaluated effects of dietary supplementation with tryptophan (Trp) on muscle growth, protein synthesis, and antioxidant capacity in hybrid catfish Pelteobagrus vachelli♀ × Leiocassis longirostris♂. Fish were fed six different diets containing 2.6 (control), 3.1, 3.7, 4.2, 4.7, and 5.6 g Trp kg−1 diet for 56 days, respectively. Results showed that dietary Trp significantly (1) improved muscle protein content, fiber density, and frequency of fiber diameter; (2) up-regulated the mRNA levels of PCNA, myf5, MyoD1, MyoG, MRF4, IGF-I, IGF-II, IGF-IR, PIK3Ca, TOR, 4EBP1, and S6K1; (3) increased phosphorylation levels of AKT, TOR, and S6K1; (4) decreased contents of MDA and PC, and increased activities of CAT, GST, GR, ASA, and AHR; (5) up-regulated mRNA levels of CuZnSOD, CAT, GST, GPx, GCLC, and Nrf2, and decreased Keap1 mRNA level; (6) increased nuclear Nrf2 protein level and the intranuclear antioxidant response element binding ability, and reduced Keap1 protein level. These results indicated that dietary Trp improved muscle growth, protein synthesis as well as antioxidant capacity, which might be partly related to myogenic regulatory factors (MRFs), IGFs/PIK3Ca/AKT/TOR, and Keap1/Nrf2 signaling pathways. Finally, based on the quadratic regression analysis of muscle protein and MDA contents, the optimal Trp requirements of hybrid catfish (21.82-39.64 g) were estimated to be 3.94 and 3.93 g Trp kg−1 diet (9.57 and 9.54 g kg−1 of dietary protein), respectively.

Endotoxin-induced decrease in muscle protein synthesis is associated with changes in eIF2B, eIF4E, and IGF-I

2000 ◽  
Vol 278 (6) ◽  
pp. E1133-E1143 ◽  
Author(s):  
Charles H. Lang ◽  
Robert A. Frost ◽  
Leonard S. Jefferson ◽  
Scot R. Kimball ◽  
Thomas C. Vary
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Translational Efficiency ◽  
Time Points ◽  
Initiation Factors ◽  
Eukaryotic Initiation Factors ◽  
Igf I ◽  
Vascular Catheters

The present study examined potential mechanisms contributing to the inhibition of protein synthesis in skeletal muscle after administration of endotoxin (LPS). Rats implanted with vascular catheters were injected intravenously with a nonlethal dose of Escherichia coli LPS, and samples were collected at 4 and 24 h thereafter; pair-fed control animals were also included. The rate of muscle (gastrocnemius) protein synthesis in vivo was reduced at both time points after LPS administration. LPS did not alter tissue RNA content, but the translational efficiency was consistently reduced at both time points. To identify mechanisms responsible for regulating translation, we examined several eukaryotic initiation factors (eIFs). The content of eIF2α or the amount of eIF2α in the phosphorylated form did not change in response to LPS. eIF2B activity was decreased in muscle 4 h post-LPS but activity returned to control values by 24 h. A decrease in the relative amount of eIF2Bα protein was not responsible for the LPS-induced reduction in eIF2B activity. LPS also markedly altered the distribution of eIF4E in muscle. Compared with control values, LPS-treated rats demonstrated 1) a transient increase in binding of the translation repressor 4E-binding protein-1 (4E-BP1) with eIF4E, 2) a transient decrease in the phosphorylated γ-form of 4E-BP1, and 3) a sustained decrease in the amount of eIF4G associated with eIF4E. LPS also decreased insulin-like growth factor (IGF) I protein and mRNA expression in muscle at both times. A significant linear relationship existed between muscle IGF-I and the rate of protein synthesis or the amount of eIF4E bound to eIF4G. In summary, these data suggest that LPS impairs muscle protein synthesis, at least in part, by decreasing translational efficiency, resulting from an impairment in translation initiation associated with alterations in both eIF2B activity and eIF4E availability.

IL-1 receptor antagonist attenuates sepsis-induced alterations in the IGF system and protein synthesis

1996 ◽  
Vol 270 (3) ◽  
pp. E430-E437 ◽  
Author(s):  
C. H. Lang ◽  
J. Fan ◽  
R. Cooney ◽  
T. C. Vary
Keyword(s):  
Protein Synthesis ◽  
Receptor Antagonist ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Abdominal Sepsis ◽  
Constant Infusion ◽  
Igf Binding Proteins ◽  
Igf System ◽  
Igf I

The purpose of the present investigation was to determine whether endogenously produced interleukin (IL)-1 mediates the changes in insulin-like growth factor (IGF) I and IGF binding proteins (IGFBP) induced by chronic abdominal sepsis in rats and to correlate the changes in the IGF system with the alternations in protein synthesis. A constant infusion of IL-1 receptor antagonist (IL-1ra) was begun after the induction of sepsis and was continued for 5 days. Sepsis decreased IGF-I levels in the blood, liver, and gastrocnemius muscle, increased the content in the kidney, and did not alter IGF-I levels in heart, jejunum, and spleen. IL-1ra attenuated the sepsis-induced decrease in plasma IGF-I and completely prevented the changes in IGF-I observed in liver, kidney, and the gastrocnemius. IGFBP-1 was increased in the blood, liver, and muscle of septic rats. IL-1ra prevented this increase in IGFBP-1 in blood and liver but not in muscle. The rate of in vivo protein synthesis was decreased in the gastrocnemius and kidney and unaltered in the heart, liver, jejunum, and spleen. A strong linear correlation existed between levels of IGF-I and the rate of protein synthesis determined simultaneously in the gastrocnemius. These results provide evidence for the role of IL-1 as an endogenous mediator of the sepsis-induced changes in IGF-I and IGFBP-1 and suggest that the accompanying changes in muscle protein synthesis are partially mediated via changes in IGF-I.

scholarly journals Acute in Vivo Elevation of Insulin-Like Growth Factor (IGF) Binding Protein-1 Decreases Plasma Free IGF-I and Muscle Protein Synthesis

Endocrinology ◽  
2003 ◽  
Vol 144 (9) ◽  
pp. 3922-3933 ◽  
Author(s):  
Charles H. Lang ◽  
Thomas C. Vary ◽  
Robert A. Frost
Keyword(s):  
Protein Synthesis ◽  
Plasma Concentration ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Binding Protein ◽  
Igf I ◽  
Igf Binding ◽  
Fast Twitch ◽  
Igf Binding Protein

Abstract This study examined whether the acute elevation of IGF-binding protein-1 (IGFBP-1) decreases the plasma free IGF-I concentration and alters in vivo rates of muscle protein synthesis and glucose uptake. The plasma concentration of human IGFBP-1 was increased to approximately 95 ng/ml in conscious catheterized rats infused iv with human IGFBP-1 for 4 h. Infusion of IGFBP-1 also increased the concentration of endogenous (e.g. rat) IGFBP-1 in the blood, and this response was associated with a 2- to 3-fold elevation of IGFBP-1 mRNA in liver and kidney. IGFBP-1 did not significantly alter the plasma concentration of total IGF-I, but decreased circulating free IGF-I levels by about 50%. IGFBP-1 decreased protein synthesis in the predominantly fast-twitch gastrocnemius muscle (20%), and this change resulted from a decreased translational efficiency that was associated with a decreased phosphorylation of S6K1, but not 4E-BP1. Complementary studies demonstrated that IGFBP-1 also decreased the rates of protein synthesis under basal conditions and in response to stimulation by IGF-I when added in vitro to the fast-twitch epitrochlearis muscle. In contrast, IGFBP-1 did not alter in vivo-determined rates of protein synthesis in the slow-twitch soleus muscle, heart, liver, or kidney. The infusion of IGFBP-1 did not significantly alter the plasma glucose or lactate concentration or the whole body rate of glucose production or disposal. The above-mentioned changes were not mediated indirectly by changes in the plasma insulin or corticosterone concentrations, decreased high energy phosphate content in muscle, or hepatoxicity produced by the infused IGFBP-1. These results demonstrate that acute in vivo elevation in IGFBP-1, of the magnitude observed in various catabolic conditions, is capable of selectively decreasing protein synthesis in fast-twitch skeletal muscle and up-regulating the hepatic and renal syntheses of IGFBP-1 per se. Hence, elevations in circulating and tissue levels of IGFBP-1 may be an important mediator for the muscle catabolism observed in various stress conditions.

Modulation of IGF mRNA abundance during stretch-induced skeletal muscle hypertrophy and regression

1994 ◽  
Vol 76 (5) ◽  
pp. 2026-2030 ◽  
Author(s):  
S. M. Czerwinski ◽  
J. M. Martin ◽  
P. J. Bechtel
Keyword(s):  
Skeletal Muscle ◽  
Muscle Hypertrophy ◽  
Muscle Protein ◽  
Muscle Growth ◽  
Mrna Abundance ◽  
Mrna Levels ◽  
Muscle Weight ◽  
Igf I ◽  
Compensatory Muscle Hypertrophy ◽  
First Time

Increased load on a muscle (synergistic overload or stretch) results in muscle hypertrophy. The expression of insulin-like growth factor I (IGF-I) mRNA in rat skeletal muscle is increased during synergistic overload-induced hypertrophy. Although it has also been established that fasting animals lose muscle protein, it has been shown that compensatory muscle hypertrophy occurs in adult fasting rats that are undergoing a net loss of body weight. The purpose of this investigation was to determine whether a relationship exists between IGF-I mRNA levels and muscle growth and regression. This was accomplished by examining whether IGF-I mRNA levels were altered during muscle hypertrophy after stretch and regression and the effect of fasting on IGF-I mRNA levels during stretch-induced hypertrophy. Patagialis (PAT) muscle weights increased 13 and 44% at 2 and 11 days of stretch, respectively. However, after removal of the stretch stimulus on day 11, PAT weights began to decrease, reaching control weights by 18 days. During the first time point (2 days), PAT muscle IGF-I mRNA remained constant. IGF-I mRNA abundance was threefold greater than contralateral control levels by 11 days of stretch. IGF-I mRNA levels decreased but remained significantly above control levels throughout the regression of hypertrophy (13, 18, and 25 days). Fasting did not alter PAT muscle response to stretch. After 11 days of stretch, PAT muscle weight increased 60% compared with contralateral control muscles and IGF-I mRNA levels increased three-fold. This study supports a role for IGF-I in muscle hypertrophy but not muscle atrophy.

scholarly journals Comprehensive assessment of post-prandial protein handling by the application of intrinsically labelled protein in vivo in human subjects

2021 ◽  
pp. 1-9
Author(s):  
Jorn Trommelen ◽  
Andrew M. Holwerda ◽  
Philippe J. M. Pinckaers ◽  
Luc J. C. van Loon
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Stable Isotope ◽  
Dietary Protein ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Human Subjects ◽  
Whole Body ◽  
Body Protein

All human tissues are in a constant state of remodelling, regulated by the balance between tissue protein synthesis and breakdown rates. It has been well-established that protein ingestion stimulates skeletal muscle and whole-body protein synthesis. Stable isotope-labelled amino acid methodologies are commonly applied to assess the various aspects of protein metabolism in vivo in human subjects. However, to achieve a more comprehensive assessment of post-prandial protein handling in vivo in human subjects, intravenous stable isotope-labelled amino acid infusions can be combined with the ingestion of intrinsically labelled protein and the collection of blood and muscle tissue samples. The combined application of ingesting intrinsically labelled protein with continuous intravenous stable isotope-labelled amino acid infusion allows the simultaneous assessment of protein digestion and amino acid absorption kinetics (e.g. release of dietary protein-derived amino acids into the circulation), whole-body protein metabolism (whole-body protein synthesis, breakdown and oxidation rates and net protein balance) and skeletal muscle metabolism (muscle protein fractional synthesis rates and dietary protein-derived amino acid incorporation into muscle protein). The purpose of this review is to provide an overview of the various aspects of post-prandial protein handling and metabolism with a focus on insights obtained from studies that have applied intrinsically labelled protein under a variety of conditions in different populations.

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