The Role of IGF-1 Signaling in Skeletal Muscle Atrophy

Timmer, Louk T.; Hoogaars, Willem M.H.; Jaspers, Richard T.

doi:10.1007/978-981-13-1435-3_6

Cited by 68 publications

(46 citation statements)

References 162 publications

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“…Conditional Cre ablation of satellite cells has led to mixed results and views on the role of satellite cell participation in the muscle growth response to overload that results from ablation of synergistic muscles (Egner et al, 2016;Lee et al, 2012;Murach et al, 2017). Among the best-described molecular mechanisms behind the control of muscle size are the insulin-like growth factor 1, transforming growth factor beta and myostatin signalling pathways (reviewed in Lee, 2004;Chen et al, 2016;Timmer et al, 2018) (see poster). Inhibition of myostatin has a dramatic effect on muscle size (Lee and McPherron, 2001), although the cellular mechanisms involved are uncertain.…”

Section: Hypertrophy Of Skeletal Musclementioning

confidence: 99%

Skeletal muscle in health and disease

Morgan

Partridge

2020

Disease Models &Amp; Mechanisms

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Skeletal muscle fibres are multinucleated cells that contain postmitotic nuclei (i.e. they are no longer able to divide) and perform muscle contraction. They are formed by fusion of muscle precursor cells, and grow into elongating myofibres by the addition of further precursor cells, called satellite cells, which are also responsible for regeneration following injury. Skeletal muscle regeneration occurs in most muscular dystrophies in response to necrosis of muscle fibres. However, the complex environment within dystrophic skeletal muscle, which includes inflammatory cells, fibroblasts and fibro-adipogenic cells, together with the genetic background of the in vivo model and the muscle being studied, complicates the interpretation of laboratory studies on muscular dystrophies. Many genes are expressed in satellite cells and in other tissues, which makes it difficult to determine the molecular cause of various types of muscular dystrophies. Here, and in the accompanying poster, we discuss our current knowledge of the cellular mechanisms that govern the growth and regeneration of skeletal muscle, and highlight the defects in satellite cell function that give rise to muscular dystrophies.

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Section: Hypertrophy Of Skeletal Musclementioning

confidence: 99%

Skeletal muscle in health and disease

Morgan

Partridge

2020

Disease Models &Amp; Mechanisms

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“…Surprisingly, we did not observe an expected decrease in IGF-1 level, but we have found an elevation of the concentration of that particular protein, but only in red muscle. However, some reports show that under certain conditions, like immobilization, muscle denervation [24], or in atrophy models induced by proinflammatory cytokines [25], IGF-1 does not prevent muscle cell atrophy, and its level may stay unaltered.…”

Section: Discussionmentioning

confidence: 99%

BST Stimulation Induces Atrophy and Changes in Aerobic Energy Metabolism in Rat Skeletal Muscles—The Biphasic Action of Endogenous Glucocorticoids

Karnia

Myślińska

Dzik

et al. 2020

IJMS

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(1) The primary involvement in stress-induced disturbances in skeletal muscles is assigned to the release of glucocorticoids (GCs). The current study aims to investigate the impact of the biphasic action of the chronic stress response (CSR) induced by the electrical stimulation of the bed nucleus of the stria terminalis (BST) effects on muscle atrophy and aerobic energy metabolism in soleus (SOL) and extensor digitorum longus (EDL) muscles. (2) Male Wistar rats (n = 17) were used. The rats were divided randomly into three groups: the BST two weeks (ST2), four weeks (ST4), and the sham (SHM) electrically stimulated group. The plasma corticosterone (CORT) and irisin concentration were measured. Glucocorticoid and mineralocorticoid receptors (GR and MR), 11β-hydroxysteroid dehydrogenase type 1 and 2 (HSD11B1 and HSD11B2), atrogin-1, and insulin-like growth factor-1 (IGF-1) level were determined in SOL and EDL muscles. Citrate synthase (CS) activity was measured in both muscles. (3) We found elevated plasma concentration of CORT and irisin, raised the level of GR in SOL muscle, and the higher level of MR in both muscles in the ST4 group. The level of HSD11B1 was also higher in the ST4 group compared to the SHM group. Moreover, we observed increased activity of CS in SOL. (4) We suggest that biphasic action of the glucocorticoid induced by the CSR occurs and causes dysregulation of proteins involved in muscle atrophy and aerobic energy metabolism. Our findings potentially contribute to a better understanding of the mechanisms by which GCs and the CSR may regulate muscle atrophy and energy preservation of the red muscle.

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Section: Introductionmentioning

confidence: 99%

“…IGF-1/IGF-1R contributes to muscle hypertrophy on untrained state mainly through activating phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)-mammalian target of rapamycin (mTOR) pathway [16][17][18], evidenced as IGF-1 induced-growth promotion of skeletal muscle could be greatly inhibited by PI3K inhibitor LY294002 or Akt inhibitor KP372-1 [19]. PI3K/Akt-mTOR pathway is activated by phosphorylating PI3K, Akt and mTOR successively after PI3K translocation to phosphorylated insulin receptor substrate 1 [18], then exerted its vital roles in regulating muscle development and hypertrophy by promoting proliferation and muscle protein synthesis and preventing muscle degradation as well [20]. Tight relationship of AR with PI3K/ Akt-mTOR pathway has been revealed by considerable amount of evidences, for example, PI3K/Akt inhibitor significantly reduced testosterone-induced muscle hypertrophy, and in turn, AR antagonist flutamide offset the increase of muscle mass caused by androgen supplementation accompanied with the decreased levels of IGF-1R and p-Akt [21,22], which indicated that androgen/AR-induced muscle hypertrophy in untrained participants was at least partly associated with the activation of IGF-1-Akt/mTOR pathway.…”

Section: Introductionmentioning

confidence: 99%

Crucial role of androgen receptor in resistance and endurance trainings-induced muscle hypertrophy through IGF-1/IGF-1R- PI3K/Akt- mTOR pathway

Yin

Lin

et al. 2020

Nutr Metab (Lond)

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Background: Androgen receptor (AR) has been reported to play vital roles in exercise-induced increase of muscle mass in rats, but needs to be further verified and the mechanism behind remains unclear. As AR target genes, insulin growth factor-1 (IGF-1) and IGF-1 receptor (IGF-1R) promote muscle hypertrophy through activating PI3K/ Akt-mammalian target of rapamycin (mTOR) pathway, a classic pathway of muscle hypertrophy. So the main purpose of this study was using AR antagonist flutamide to demonstrate AR's effect on training-induced muscle hypertrophy and its possible mechanism: IGF-1/IGF-1R-PI3K/Akt-mTOR pathway? Methods: Forty-eight Sprague Dawley male rats aged 7 weeks were randomly divided into six groups: control (C), flutamide (F), resistance training (R), resistance training plus flutamide (R + F), endurance training (E), and endurance training plus flutamide (E + F) groups. Flutamide was used to block AR in rats. Rats in R and R + F groups fulfilled 3 weeks of ladder climbing with progressively increased load, while E and E + F rats completed 3-week moderate intensity aerobic exercise on a treadmill. The relative muscle mass (muscle mass/body weight) of rats was detected. Serum levels of testosterone and IGF-1 of rats were determined by ELISA, and mRNA levels of IGF-1R and mTOR in muscles by real-time PCR. Protein levels of AR, IGF-1, IGF-1R, mTOR, PI3K, Akt, p-PI3K and p-Akt in muscles were detected by Western blot. Results: (1) The training-induced rise in the relative muscle mass and the expression levels of AR were only found in the gastrocnemius of R rats and in the soleus of E rats (selective muscle hypertrophy), which were blocked by flutamide. (2) Serum testosterone in the R and E rat were increased, and flutamide exerted no effect. (3) The levels of IGF-1, IGF-1R and mTOR as well as the activities of PI3K and Akt were enhanced selectively (in the gastrocnemius of R rats and in the soleus of E rats), which were reduced by flutamide. Conclusions: AR exerted an essential role in both resistance training and endurance training-induced muscle hypertrophy, which was mediated at least partly through IGF-1/IGF-1R-PI3K/Akt-mTOR pathway.

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The Role of IGF-1 Signaling in Skeletal Muscle Atrophy

Cited by 68 publications

References 162 publications

Skeletal muscle in health and disease

Skeletal muscle in health and disease

BST Stimulation Induces Atrophy and Changes in Aerobic Energy Metabolism in Rat Skeletal Muscles—The Biphasic Action of Endogenous Glucocorticoids

Crucial role of androgen receptor in resistance and endurance trainings-induced muscle hypertrophy through IGF-1/IGF-1R- PI3K/Akt- mTOR pathway

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