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 language | English (US) |
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Pages (from-to) | 464-473 |
Number of pages | 10 |
Journal | Muscle and Nerve |
Volume | 60 |
Issue number | 4 |
DOIs | |
State | Published - Oct 1 2019 |
Externally published | Yes |
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)