Improved contractile function of the mdx dystrophic mouse diaphragm muscle after insulin-like growth factor-I administration.

Abstract

Limited knowledge exists regarding the efficacy of insulin-like growth factor I (IGF-I) administration as a therapeutic intervention for muscular dystrophies, although findings from other muscle pathology models suggest clinical potential. The diaphragm muscles of mdx mice (a model for Duchenne muscular dystrophy) were examined after 8 weeks of IGF-I administration (1 mg/kg s.c.) to test the hypothesis that IGF-I would improve the functional properties of dystrophic skeletal muscles. Force per cross-sectional area was approximately 49% greater in the muscles of treated mdx mice (149.6 +/- 9.6 kN/m(2)) compared with untreated mice (100.1 +/- 4.6 kN/m(2), P < 0.05), and maintenance of force over repeated maximal contraction was enhanced approximately 30% in muscles of treated mice (P < 0.05). Diaphragm muscles from treated mice comprised fibers with approximately 36% elevated activity of the oxidative enzyme succinate dehydrogenase, and approximately 23% reduction in the proportion of fast IId/x muscle fibers with concomitant increase in the proportion of type IIa fibers compared with untreated mice (P < 0.05). The data demonstrate that IGF-I administration can enhance the fatigue resistance of respiratory muscles in an animal model of dystrophin deficiency, in conjunction with enhancing energenic enzyme activity. As respiratory function is a mortality predictor in Duchenne muscular dystrophy patients, further evaluation of IGF-I intervention is recommended.

• Authors: Paul Gregorevic, David R Plant, Kerri S Leeding, Leon A Bach, Gordon S Lynch
• Journal: The American journal of pathology (Am J Pathol) Vol. 161 Issue 6 Pg. 2263-72 (Dec 2002) ISSN: 0002-9440 [Print] United States
• PMID: 12466140 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin-Like Growth Factor I
• Succinate Dehydrogenase

Topics

• Animals
• Diaphragm (cytology, drug effects, physiology)
• Electric Stimulation
• Humans
• In Vitro Techniques
• Insulin-Like Growth Factor I (administration & dosage, pharmacology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Inbred mdx
• Muscle Contraction (physiology)
• Muscular Dystrophy, Animal (physiopathology)
• Muscular Dystrophy, Duchenne (physiopathology)
• Random Allocation
• Succinate Dehydrogenase (metabolism)