Insulin-like growth factor I slows the rate of denervation induced skeletal muscle atrophy

• Published in: Neuromuscular disorders : NMD Vol. 15; no. 2; pp. 139 - 146
• Main Authors: Shavlakadze, Thea, White, Jason D., Davies, Marilyn, Hoh, Joseph F.Y., Grounds, Miranda D.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01-02-2005
• Subjects: Animals; Atrophy; Body Weight - physiology; Cell Size; Denervation; Disease Models, Animal; Disease Progression; Down-Regulation - physiology; IGF-1; Insulin-Like Growth Factor I - genetics; Mice; Mice, Transgenic; Muscle Fibers, Skeletal - metabolism; Muscle Fibers, Skeletal - pathology; Muscle Proteins - metabolism; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscle, Skeletal - physiopathology; Muscular Atrophy - genetics; Muscular Atrophy - metabolism; Muscular Atrophy - physiopathology; Sciatic Neuropathy - complications; Sciatic Neuropathy - pathology; Sciatic Neuropathy - physiopathology; Skeletal muscle; Time Factors; Transgenic mouse; Up-Regulation - physiology; Atrophy; Transgenic mouse; IGF-1; Skeletal muscle; Denervation
• ISSN: 0960-8966; 1873-2364
• DOI: 10.1016/j.nmd.2004.10.013

Loss of the nerve supply to skeletal muscle results in a relentless loss of muscle mass (atrophy) over time. The ability of insulin-like growth factor-1 to reduce atrophy resulting from denervation was examined after transection of the sciatic nerve in transgenic MLC/mIGF-1 mice that over-express mIGF-1 specifically in differentiated myofibres. The cross sectional area (CSA) of all types of myofibres and specifically type IIB myofibres was measured in tibialis anterior muscles from transgenic and wild-type mice at 28 days after denervation. There was a marked myofibre atrophy (∼60%) in the muscles of wild-type mice over this time with increased numbers of myofibres with small CSA. In the muscles of MLC/mIGF-1 mice, over-expression of mIGF-1 reduced the rate of denervation induced myofibre atrophy by ∼30% and preserved myofibres with larger CSA, compared to wild-type muscles. It is proposed that the protective effect of mIGF-1 on denervated myofibres might be due to reduced protein breakdown.