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.

Activation of insulin-like growth factor gene expression during work-induced skeletal muscle growth

1990 ◽  
Vol 259 (1) ◽  
pp. E89-E95 ◽  
Author(s):  
D. L. DeVol ◽  
P. Rotwein ◽  
J. L. Sadow ◽  
J. Novakofski ◽  
P. J. Bechtel
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Factor ◽  
Muscle Growth ◽  
Experimental Period ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Muscle Weight ◽  
Skeletal Muscle Growth ◽  
Igf I

We have investigated the hypothesis that there is local regulation of insulin-like growth factor (IGF) gene expression during skeletal muscle growth. Compensatory hypertrophy was induced in the soleus, a predominantly slow-twitch muscle, and plantaris, a fast-twitch muscle, in 11- to 12-wk-old female Wistar rats by unilateral cutting of the distal gastrocnemius tendon. Animals were killed 2, 4, or 8 days later, and muscles of the nonoperated leg served as controls. Muscle weight increased throughout the experimental period, reaching 127% (soleus) or 122% (plantaris) of control values by day 8. In both growing muscles, IGF-I mRNA, quantitated by a solution-hybridization nuclease-protection assay, rose by nearly threefold on day 2 and remained elevated throughout the experimental period. IGF-II mRNA levels also increased over controls. A more dramatic response was seen in hypophysectomized rats, where IGF-I mRNA levels rose by 8- to 13-fold, IGF-II values by 3- to 7-fold, and muscle mass increased on day 8 to 149% (soleus) or 133% (plantaris) of the control contralateral limb. These results indicate that signals propagated during muscle hypertrophy enhance the expression of both IGF genes, that modulation of IGF-I mRNA levels can occur in the absence of growth hormone, and that locally produced IGF-I and IGF-II may play a role in skeletal muscle growth.

Induction of mRNA for IGF-I and -II during growth hormone-stimulated muscle hypertrophy

1988 ◽  
Vol 255 (4) ◽  
pp. E513-E517 ◽  
Author(s):  
J. D. Turner ◽  
P. Rotwein ◽  
J. Novakofski ◽  
P. J. Bechtel
Keyword(s):  
Skeletal Muscle ◽  
Growth Hormone ◽  
Growth Factors ◽  
Cardiac Muscle ◽  
Muscle Hypertrophy ◽  
Muscle Growth ◽  
Gh3 Cells ◽  
Autocrine Factors ◽  
Igf I ◽  
Steady State Levels

The expression of insulin-like growth factor (IGF) genes during skeletal and cardiac muscle hypertrophy was examined using skeletal and cardiac muscle hypertrophy was examined using adult 5-mo-old female Wistar-Furth rats implanted with growth hormone-secreting GH3 cells. Control and treated animals were killed at 40, 60, and 80 days after initiation of the experiment. From the time of injection to day 80, body, heart, skeletal muscle, and liver weights increased 112, 93, 55, and 314%, respectively. RNA was extracted and steady-state levels of IGF-I and IGF-II mRNAs were quantitated using a solution-hybridization nuclease-protection assay. Low levels of mRNA for both growth factors were detected in control tissues. By day 80 IGF-I mRNA had increased eightfold and IGF-II mRNA sixfold in skeletal muscle from treated rats. In cardiac muscle the levels of mRNA for both growth factors rose three- to fourfold. Although growth hormone induced an increase in hepatic IGF-I mRNA, IGF-II mRNA remained nearly undetectable. This study shows that during growth hormone-stimulated muscle growth mRNAs for both IGF-I and IGF-II accumulate, supporting other observations implicating the IGFs as paracrine or autocrine factors involved in skeletal muscle growth.

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.

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.

Hypoxia transiently affects skeletal muscle hypertrophy in a functional overload model

2012 ◽  
Vol 302 (5) ◽  
pp. R643-R654 ◽  
Author(s):  
Thomas Chaillou ◽  
Nathalie Koulmann ◽  
Nadine Simler ◽  
Adélie Meunier ◽  
Bernard Serrurier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Muscle Hypertrophy ◽  
Molecular Mechanisms ◽  
Muscle Growth ◽  
Female Rats ◽  
Mrna Levels ◽  
Hypertrophic Response ◽  
Protein Levels ◽  
Skeletal Muscle Hypertrophy

Hypoxia induces a loss of skeletal muscle mass, but the signaling pathways and molecular mechanisms involved remain poorly understood. We hypothesized that hypoxia could impair skeletal muscle hypertrophy induced by functional overload (Ov). To test this hypothesis, plantaris muscles were overloaded during 5, 12, and 56 days in female rats exposed to hypobaric hypoxia (5,500 m), and then, we examined the responses of specific signaling pathways involved in protein synthesis (Akt/mTOR) and breakdown (atrogenes). Hypoxia minimized the Ov-induced hypertrophy at days 5 and 12 but did not affect the hypertrophic response measured at day 56. Hypoxia early reduced the phosphorylation levels of mTOR and its downstream targets P70S6K and rpS6, but it did not affect the phosphorylation levels of Akt and 4E-BP1, in Ov muscles. The role played by specific inhibitors of mTOR, such as AMPK and hypoxia-induced factors (i.e., REDD1 and BNIP-3) was studied. REDD1 protein levels were reduced by overload and were not affected by hypoxia in Ov muscles, whereas AMPK was not activated by hypoxia. Although hypoxia significantly increased BNIP-3 mRNA levels at day 5, protein levels remained unaffected. The mRNA levels of the two atrogenes MURF1 and MAFbx were early increased by hypoxia in Ov muscles. In conclusion, hypoxia induced a transient alteration of muscle growth in this hypertrophic model, at least partly due to a specific impairment of the mTOR/P70S6K pathway, independently of Akt, by an undefined mechanism, and increased transcript levels for MURF1 and MAFbx that could contribute to stimulate the proteasomal proteolysis.

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.

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.

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 Role of IGF-I in follistatin-induced skeletal muscle hypertrophy

2015 ◽  
Vol 309 (6) ◽  
pp. E557-E567 ◽  
Author(s):  
Caroline Barbé ◽  
Stéphanie Kalista ◽  
Audrey Loumaye ◽  
Olli Ritvos ◽  
Pascale Lause ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Muscle Hypertrophy ◽  
Muscle Growth ◽  
Skeletal Muscle Hypertrophy ◽  
Low Concentrations ◽  
Igf I

Follistatin, a physiological inhibitor of myostatin, induces a dramatic increase in skeletal muscle mass, requiring the type 1 IGF-I receptor/Akt/mTOR pathway. The aim of the present study was to investigate the role of IGF-I and insulin, two ligands of the IGF-I receptor, in the follistatin hypertrophic action on skeletal muscle. In a first step, we showed that follistatin increases muscle mass while being associated with a downregulation of muscle IGF-I expression. In addition, follistatin retained its full hypertrophic effect toward muscle in hypophysectomized animals despite very low concentrations of circulating and muscle IGF-I. Furthermore, follistatin did not increase muscle sensitivity to IGF-I in stimulating phosphorylation of Akt but, surprisingly, decreased it once hypertrophy was present. Taken together, these observations indicate that increased muscle IGF-I production or sensitivity does not contribute to the muscle hypertrophy caused by follistatin. Unlike low IGF-I, low insulin, as obtained by streptozotocin injection, attenuated the hypertrophic action of follistatin on skeletal muscle. Moreover, the full anabolic response to follistatin was restored in this condition by insulin but also by IGF-I infusion. Therefore, follistatin-induced muscle hypertrophy requires the activation of the insulin/IGF-I pathway by either insulin or IGF-I. When insulin or IGF-I alone is missing, follistatin retains its full anabolic effect, but when both are deficient, as in streptozotocin-treated animals, follistatin fails to stimulate muscle growth.

scholarly journals Effects of spaceflight and thyroid deficiency on hindlimb development. I. Muscle mass and IGF-I expression

2000 ◽  
Vol 88 (3) ◽  
pp. 894-903 ◽  
Author(s):  
G. R. Adams ◽  
S. A. McCue ◽  
P. W. Bodell ◽  
M. Zeng ◽  
K. M. Baldwin
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Muscle Growth ◽  
Somatic Growth ◽  
The Body ◽  
Neonatal Rats ◽  
Muscle Weight ◽  
Skeletal Muscle Growth ◽  
Igf I ◽  
The Impact

Thyroid deficiency (TD) in neonatal rats causes reduced growth of skeletal muscle that is disproportionately greater than that for other tissues (G. R. Adams, S. A. McCue, M. Zeng, and K. M. Baldwin. Am. J. Physiol. Regulatory Integrative Comp. Physiol. 276: R954–R961, 1999). TD depresses plasma insulin-like growth factor I (IGF-I) levels, suggesting a mechanism for this effect. We hypothesized that TD and exposure to spaceflight (SF) would interact to reduce skeletal muscle growth via a reduction in IGF-I levels. Neonatal rats were flown in space for 16 days. There was a similar, nonadditive reduction in the growth of the body (∼50%) and muscle weight (fast muscles, ∼60%) with either TD or SF. In the soleus muscle, either SF or TD alone resulted in growth reductions that were augmented by SF-TD interactions. There were strong correlations between 1) muscle mass and muscle IGF-I levels and 2) circulating IGF-I and body weight. These results indicate that either hypothyroidism or exposure to SF will limit the somatic and muscle-specific growth of neonatal rats. The impact of these perturbations on skeletal muscle growth is relatively greater than the effect on somatic growth. The mechanisms by which either TD or SF impact growth appear to have a common pathway involving the control of plasma and muscle IGF-I concentrations.

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