scholarly journals Localized infusion of IGF-I results in skeletal muscle hypertrophy in rats

1998 ◽  
Vol 84 (5) ◽  
pp. 1716-1722 ◽  
Author(s):  
Gregory R. Adams ◽  
Samuel A. McCue
Keyword(s):  
Skeletal Muscle ◽  
Dna Content ◽  
Muscle Hypertrophy ◽  
Muscle Protein ◽  
Weight Bearing ◽  
Muscle Size ◽  
Heart Weight ◽  
Protein Ratio ◽  
Skeletal Muscle Hypertrophy ◽  
Igf I

Insulin-like growth factor I (IGF-I) peptide levels have been shown to increase in overloaded skeletal muscles (G. R. Adams and F. Haddad. J. Appl. Physiol. 81: 2509–2516, 1996). In that study, the increase in IGF-I was found to precede measurable increases in muscle protein and was correlated with an increase in muscle DNA content. The present study was undertaken to test the hypothesis that direct IGF-I infusion would result in an increase in muscle DNA as well as in various measurements of muscle size. Either 0.9% saline or nonsystemic doses of IGF-I were infused directly into a non-weight-bearing muscle of rats, the tibialis anterior (TA), via a fenestrated catheter attached to a subcutaneous miniosmotic pump. Saline infusion had no effect on the mass, protein content, or DNA content of TA muscles. Local IGF-I infusion had no effect on body or heart weight. The absolute weight of the infused TA muscles was ∼9% greater ( P < 0.05) than that of the contralateral TA muscles. IGF-I infusion resulted in significant increases in the total protein and DNA content of TA muscles ( P < 0.05). As a result of these coordinated changes, the DNA-to-protein ratio of the hypertrophied TA was similar to that of the contralateral muscles. These results suggest that IGF-I may be acting to directly stimulate processes such as protein synthesis and satellite cell proliferation, which result in skeletal muscle hypertrophy.

scholarly journals Stimuli and sensors that initiate skeletal muscle hypertrophy following resistance exercise

2019 ◽  
Vol 126 (1) ◽  
pp. 30-43 ◽  
Author(s):  
Henning Wackerhage ◽  
Brad J. Schoenfeld ◽  
D. Lee Hamilton ◽  
Maarit Lehti ◽  
Juha J. Hulmi
Keyword(s):  
Skeletal Muscle ◽  
Resistance Exercise ◽  
Muscle Damage ◽  
Muscle Hypertrophy ◽  
Muscle Protein ◽  
Large Body ◽  
Focal Adhesions ◽  
Indirect Evidence ◽  
Skeletal Muscle Hypertrophy ◽  
Exercise Induced

One of the most striking adaptations to exercise is the skeletal muscle hypertrophy that occurs in response to resistance exercise. A large body of work shows that a mammalian target of rapamycin complex 1 (mTORC1)-mediated increase of muscle protein synthesis is the key, but not sole, mechanism by which resistance exercise causes muscle hypertrophy. While much of the hypertrophy signaling cascade has been identified, the initiating, resistance exercise-induced and hypertrophy-stimulating stimuli have remained elusive. For the purpose of this review, we define an initiating, resistance exercise-induced and hypertrophy-stimulating signal as “hypertrophy stimulus,” and the sensor of such a signal as “hypertrophy sensor.” In this review we discuss our current knowledge of specific mechanical stimuli, damage/injury-associated and metabolic stress-associated triggers, as potential hypertrophy stimuli. Mechanical signals are the prime hypertrophy stimuli candidates, and a filamin-C-BAG3-dependent regulation of mTORC1, Hippo, and autophagy signaling is a plausible albeit still incompletely characterized hypertrophy sensor. Other candidate mechanosensing mechanisms are nuclear deformation-initiated signaling or several mechanisms related to costameres, which are the functional equivalents of focal adhesions in other cells. While exercise-induced muscle damage is probably not essential for hypertrophy, it is still unclear whether and how such muscle damage could augment a hypertrophic response. Interventions that combine blood flow restriction and especially low load resistance exercise suggest that resistance exercise-regulated metabolites could be hypertrophy stimuli, but this is based on indirect evidence and metabolite candidates are poorly characterized.

scholarly journals Exercise-Induced Muscle Damage and Hypertrophy: A Closer Look Reveals the Jury is Still Out

2018 ◽  
Author(s):  
Brad Jon Schoenfeld ◽  
Bret Contreras
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Resistance Training ◽  
Muscle Damage ◽  
Muscle Hypertrophy ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Skeletal Muscle Hypertrophy ◽  
Exercise Induced

This letter is a response to the paper by Damas et al (2017) titled, “The development of skeletal muscle hypertrophy through resistance training: the role of muscle damage and muscle protein synthesis,” which, in part, endeavored to review the role of exercise-induced muscle damage on muscle hypertrophy. We feel there are a number of issues in interpretation of research and extrapolation that preclude drawing the inference expressed in the paper that muscle damage neither explains nor potentiates increases in muscle hypertrophy. The intent of our letter is not to suggest that a causal role exists between hypertrophy and microinjury. Rather, we hope to provide balance to the evidence presented and offer the opinion that the jury is still very much out as to providing answers on the topic.

Viral expression of insulin-like growth factor-I isoforms promotes different responses in skeletal muscle

2006 ◽  
Vol 100 (6) ◽  
pp. 1778-1784 ◽  
Author(s):  
Elisabeth R. Barton
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Muscle Mass ◽  
Muscle Hypertrophy ◽  
Muscle Development ◽  
Muscle Size ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Insulin-like growth factor I (IGF-I) is a critical protein for skeletal muscle development and regeneration. Its ability to promote skeletal muscle hypertrophy has been demonstrated by several methods. Alternative splicing of the Igf-1 gene does not affect the mature IGF-I protein but does produce different E peptide extensions, which have been reported to modify the potency of IGF-I. Viral-mediated delivery of murine IGF-IA and IGF-IB into skeletal muscle of 2-wk-old and 6-mo-old mice was utilized to compare the effects of the isoforms on muscle mass. In young mice, tissue content of IGF-I protein was significantly higher in rAAV-treated muscles than control muscles at 1, 2, and 4 mo postinjection. Viral injection of IGF-IB produced two- to sevenfold more IGF-I than rAAVIGF-IA. Hypertrophy was observed 2 and 4 mo postinjection, where both rAAVIGF-IA and rAAVIGF-IB were equally effective in increasing muscle mass. These results suggest that there is a threshold of IGF-I production necessary to promote muscle hypertrophy in young growing animals regardless of isoform. In 6-mo-old animals, only rAAVIGF-IA produced significant increases in muscle size, even though increased IGF-I content was observed after injection of both isoforms. Therefore, the ability for IGF-IB to promote muscle hypertrophy is only effective in growing animals, suggesting that the bioavailability of this isoform or its receptor affinity diminishes with age.

scholarly journals The relationships among IGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy

1996 ◽  
Vol 81 (6) ◽  
pp. 2509-2516 ◽  
Author(s):  
G. R. Adams ◽  
F. Haddad
Keyword(s):  
Skeletal Muscle ◽  
Dna Content ◽  
Time Course ◽  
Muscle Hypertrophy ◽  
Weight Ratio ◽  
Surgical Removal ◽  
Protein Accumulation ◽  
Hypertrophic Response ◽  
Skeletal Muscle Hypertrophy ◽  
Strong Positive Relationship

Adams, G. R., and F. Haddad. The relationships among IGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy. J. Appl. Physiol. 81(6): 2509–2516, 1996.—Insulin-like growth factor-1 (IGF-1) is known to have anabolic effects on skeletal muscle cells. This study examined the time course of muscle hypertrophy and associated IGF-1 peptide and mRNA expression. Data were collected at 3, 7, 14, and 28 days after surgical removal of synergistic muscles of both normal and hypophysectomized (HX) animals. Overloading increased the plantaris (Plant) mass, myofiber size, and protein-to-body weight ratio in both groups (normal and HX; P < 0.05). Muscle IGF-1 peptide levels peaked at 3 (normal) and 7 (HX) days of overloading with maximum 4.1-fold (normal) and 6.2-fold (HX) increases. Increases in muscle IGF-1 preceded the hypertrophic response. Total DNA content of the overloaded Plant increased in both groups. There was a strong positive relationship between IGF-1 peptide and DNA content in the overloaded Plant from both groups. These results indicate that 1) the muscles from rats with both normal and severely depressed systemic levels of IGF-1 respond to functional overload with an increase in local IGF-1 expression and 2) this elevated IGF-1 may be contributing to the hypertrophy response, possibly via the mobilization of satellite cells to provide increases in muscle DNA.

scholarly journals Insulin-like growth factor (IGF-I) induces myotube hypertrophy associated with an increase in anaerobic glycolysis in a clonal skeletal-muscle cell model

1999 ◽  
Vol 339 (2) ◽  
pp. 443-451 ◽  
Author(s):  
Christopher SEMSARIAN ◽  
Pramod SUTRAVE ◽  
David R. RICHMOND ◽  
Robert M. GRAHAM
Keyword(s):  
Skeletal Muscle ◽  
Muscle Hypertrophy ◽  
Cell Model ◽  
Muscle Growth ◽  
C2c12 Cells ◽  
Anaerobic Glycolysis ◽  
Skeletal Muscle Hypertrophy ◽  
Igf I ◽  
Control Myotubes ◽  
Myotube Hypertrophy

Insulin-like growth factor-I (IGF-I) is an important autocrine/paracrine mediator of skeletal-muscle growth and development. To develop a definitive cultured cell model of skeletal-muscle hypertrophy, C2C12 cells were stably transfected with IGF-I and clonal lines developed and evaluated. Quantitative morphometric analysis showed that IGF-I-transfected myotubes had a larger area (2381±60 µm2 versus 1429±39 µm2; P< 0.0001) and a greater maximum width (21.4±0.6 µm versus 13.9±0.3 µm; P< 0.0001) than control C2C12 myotubes, independent of the number of cell nuclei per myotube. IGF-I-transfected myotubes had higher levels of protein synthesis but no difference in DNA synthesis when compared with control myotubes, indicating the development of hypertrophy rather than hyperplasia. Both lactate dehydrogenase and alanine aminotransferase activities were increased (3- and 5-fold respectively), and total lactate levels were higher (2.3-fold) in IGF-I-transfected compared with control myotubes, indicating an increase in anaerobic glycolysis in the hypertrophied myotubes. However, expression of genes involved in skeletal-muscle growth or hypertrophy in vivo, e.g. myocyte nuclear factor and myostatin, was not altered in the IGF-I myotubes. Finally, myotube hypertrophy could also be induced by treatment of C2C12 cells with recombinant IGF-I or by growing C2C12 cells in conditioned media from IGF-I-transfected cells. This quantitative model should be uniquely useful for elucidating the molecular mechanisms of skeletal-muscle hypertrophy.

Serum IGF-I-Deficiency Does Not Prevent Compensatory Skeletal Muscle Hypertrophy in Resistance Exercise

2009 ◽  
Vol 234 (2) ◽  
pp. 164-170 ◽  
Author(s):  
Wayne Matheny ◽  
Edward Merritt ◽  
Symeon V. Zannikos ◽  
Roger P. Farrar ◽  
Martin L. Adamo
Keyword(s):  
Skeletal Muscle ◽  
Resistance Exercise ◽  
Muscle Hypertrophy ◽  
Skeletal Muscle Hypertrophy ◽  
Igf I

ANG II is required for optimal overload-induced skeletal muscle hypertrophy

2001 ◽  
Vol 280 (1) ◽  
pp. E150-E159 ◽  
Author(s):  
Scott E. Gordon ◽  
Bradley S. Davis ◽  
Christian J. Carlson ◽  
Frank W. Booth
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Muscle Hypertrophy ◽  
Ace Inhibitor ◽  
Muscle Protein ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Surgical Ablation ◽  
Hypertrophic Response ◽  
Skeletal Muscle Hypertrophy

ANG II mediates the hypertrophic response of overloaded cardiac muscle, likely via the ANG II type 1 (AT1) receptor. To examine the potential role of ANG II in overload-induced skeletal muscle hypertrophy, plantaris and/or soleus muscle overload was produced in female Sprague-Dawley rats (225–250 g) by the bilateral surgical ablation of either the synergistic gastrocnemius muscle ( experiment 1) or both the gastrocnemius and plantaris muscles ( experiment 2). In experiment 1 ( n = 10/ group), inhibiting endogenous ANG II production by oral administration of an angiotensin-converting enzyme (ACE) inhibitor during a 28-day overloading protocol attenuated plantaris and soleus muscle hypertrophy by 57 and 96%, respectively (as measured by total muscle protein content). ACE inhibition had no effect on nonoverloaded (sham-operated) muscles. With the use of new animals ( experiment 2; n = 8/group), locally perfusing overloaded soleus muscles with exogenous ANG II (via osmotic pump) rescued the lost hypertrophic response in ACE-inhibited animals by 71%. Furthermore, orally administering an AT1 receptor antagonist instead of an ACE inhibitor produced a 48% attenuation of overload-induced hypertrophy that could not be rescued by ANG II perfusion. Thus ANG II may be necessary for optimal overload-induced skeletal muscle hypertrophy, acting at least in part via an AT1receptor-dependent pathway.

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