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

Abstract

IntroductionDysferlin 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.MethodsMuscle‐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.ResultsMuscle 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.DiscussionWe conclude that increased local IGF‐1 promotes functional hypertrophy when dysferlin is absent and reestablishes IGF‐1 as a potential therapeutic for dysferlinopathies.