The role of IGF-1 signaling in skeletal muscle atrophy

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

Research output: Chapter in Book / Report / Conference proceedingChapterAcademicpeer-review

Abstract

Insulin-like growth factor 1 (IGF-1) is a key anabolic growth factor stimulating phosphatidylinositol 3-kinase (PI3K)/Akt signaling which is well known for regulating muscle hypertrophy. However, the role of IGF-1 in muscle atrophy is less clear. This review provides an overview of the mechanisms via which IGF-1 signaling is implicated in several conditions of muscle atrophy and via which mechanisms protein turnover is altered. IGF-1/PI3K/Akt signaling stimulates the rate of protein synthesis via p70S6Kinase and p90 ribosomal S6 kinase and negatively regulates protein degradation, predominantly by its inhibiting effect on proteasomal and lysosomal protein degradation. Caspase-dependent protein degradation is also attenuated by IGF/PI3K/Akt signaling, whereas evidence for an effect on calpain-dependent protein degradation is inconclusive. IGF-1/PI3K/Akt signaling reduces during denervation-, unloading-, and joint immobilization-induced muscle atrophy, whereas IGF-1/PI3K/Akt signaling seems unaltered during aging-associated muscle atrophy. During denervation and aging, IGF-1 overexpression or injection counteracts denervation- and aging-associated muscle atrophy, despite enhanced anabolic resistance with regard to IGF-1 signaling with aging. It remains unclear whether pharmacological stimulation of IGF-1/PI3K/Akt signaling attenuates immobilization- or unloading-induced muscle atrophy. Exploration of the possibilities to interfere with IGF-1/PI3K/Akt signaling reveals that microRNAs targeting IGF-1 signaling components are promising targets to counterbalance muscle atrophy. Overall, the findings summarized in this review show that in disuse conditions, but not with aging, IGF-1/PI3K/Akt signaling is attenuated and that in some conditions stimulation of this pathway may alleviate skeletal muscle atrophy.

Original languageEnglish
Title of host publicationMuscle atrophy
PublisherSpringer New York LLC
Pages109-137
Number of pages29
Volume1088
ISBN (Electronic)9789811314353
ISBN (Print)9789811314346
DOIs
Publication statusPublished - 2018

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1088
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Fingerprint

Muscular Atrophy
Somatomedins
Phosphatidylinositol 3-Kinase
Muscle
Skeletal Muscle
Aging of materials
Proteolysis
Denervation
Degradation
Proteins
Unloading
Immobilization
90-kDa Ribosomal Protein S6 Kinases
Calpain
Caspases
MicroRNAs
Hypertrophy
Intercellular Signaling Peptides and Proteins
Joints
Pharmacology

Keywords

  • Aging
  • Calpain
  • Caspase
  • Disuse
  • Hypertrophy
  • Lysosome
  • miRNA

Cite this

Timmer, L. T., Hoogaars, W. M. H., & Jaspers, R. T. (2018). The role of IGF-1 signaling in skeletal muscle atrophy. In Muscle atrophy (Vol. 1088, pp. 109-137). (Advances in Experimental Medicine and Biology; Vol. 1088). Springer New York LLC. https://doi.org/10.1007/978-981-13-1435-3_6
Timmer, Louk T. ; Hoogaars, Willem M.H. ; Jaspers, Richard T. / The role of IGF-1 signaling in skeletal muscle atrophy. Muscle atrophy. Vol. 1088 Springer New York LLC, 2018. pp. 109-137 (Advances in Experimental Medicine and Biology).
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Timmer, LT, Hoogaars, WMH & Jaspers, RT 2018, The role of IGF-1 signaling in skeletal muscle atrophy. in Muscle atrophy. vol. 1088, Advances in Experimental Medicine and Biology, vol. 1088, Springer New York LLC, pp. 109-137. https://doi.org/10.1007/978-981-13-1435-3_6

The role of IGF-1 signaling in skeletal muscle atrophy. / Timmer, Louk T.; Hoogaars, Willem M.H.; Jaspers, Richard T.

Muscle atrophy. Vol. 1088 Springer New York LLC, 2018. p. 109-137 (Advances in Experimental Medicine and Biology; Vol. 1088).

Research output: Chapter in Book / Report / Conference proceedingChapterAcademicpeer-review

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Timmer LT, Hoogaars WMH, Jaspers RT. The role of IGF-1 signaling in skeletal muscle atrophy. In Muscle atrophy. Vol. 1088. Springer New York LLC. 2018. p. 109-137. (Advances in Experimental Medicine and Biology). https://doi.org/10.1007/978-981-13-1435-3_6