Functional muscle hypertrophy by increased insulin-like growth factor 1 does not require dysferlin

Elisabeth R. Barton, Jennifer Pham, Becky K. Brisson, Soo Hyun Park, Lucas R. Smith, Min Liu, Zuozhen Tian, David W. Hammers, Georgios Vassilakos, H. Lee Sweeney

Research output: Contribution to journalArticle

Abstract

Introduction: Dysferlin loss-of-function mutations cause muscular dystrophy, accompanied by impaired membrane repair and muscle weakness. Growth promoting strategies including insulin-like growth factor 1 (IGF-1) could provide benefit but may cause strength loss or be ineffective. The objective of this study was to determine whether locally increased IGF-1 promotes functional muscle hypertrophy in dysferlin-null (Dysf−/−) mice. Methods: Muscle-specific transgenic expression and postnatal viral delivery of Igf1 were used in Dysf−/− and control mice. Increased IGF-1 levels were confirmed by enzyme-linked immunosorbent assay. Testing for skeletal muscle mass and function was performed in male and female mice. Results: Muscle hypertrophy occurred in response to increased IGF-1 in mice with and without dysferlin. Male mice showed a more robust response compared with females. Increased IGF-1 did not cause loss of force per cross-sectional area in Dysf−/− muscles. Discussion: We conclude that increased local IGF-1 promotes functional hypertrophy when dysferlin is absent and reestablishes IGF-1 as a potential therapeutic for dysferlinopathies.

Original languageEnglish (US)
Pages (from-to)464-473
Number of pages10
JournalMuscle and Nerve
Volume60
Issue number4
DOIs
StatePublished - Oct 1 2019
Externally publishedYes

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Keywords

  • dysferlin
  • insulin-like growth factor 1
  • Miyoshi myopathy
  • muscle hypertrophy
  • skeletal muscle function

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)

Cite this

Barton, E. R., Pham, J., Brisson, B. K., Park, S. H., Smith, L. R., Liu, M., Tian, Z., Hammers, D. W., Vassilakos, G., & Sweeney, H. L. (2019). Functional muscle hypertrophy by increased insulin-like growth factor 1 does not require dysferlin. Muscle and Nerve, 60(4), 464-473. https://doi.org/10.1002/mus.26641