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

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.

• Authors: Elisabeth R Barton, Jennifer Pham, Becky K Brisson, SooHyun Park, Lucas R Smith, Min Liu, Zuozhen Tian, David W Hammers, Georgios Vassilakos, H Lee Sweeney
• Journal: Muscle & nerve (Muscle Nerve) Vol. 60 Issue 4 Pg. 464-473 (10 2019) ISSN: 1097-4598 [Electronic] United States
• PMID: 31323135 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2019 The Authors. Muscle & Nerve published by Wiley Periodicals, Inc.

Chemical References

• Dysf protein, mouse
• Dysferlin
• insulin-like growth factor-1, mouse
• Insulin-Like Growth Factor I

Topics

• Animals
• Diaphragm (metabolism, pathology)
• Dysferlin (genetics)
• Insulin-Like Growth Factor I (genetics)
• Mice
• Mice, Knockout
• Mice, Transgenic
• Muscle, Skeletal (metabolism, pathology)
• Muscular Dystrophies (genetics)
• Organ Size