Insulin growth factor-1 decreases muscle atrophy following denervation.
Despite modern microsurgical techniques for nerve repair, functional outcome following proximal injury is often unsatisfactory because irreversible muscle atrophy may develop before reinnervation occurs. Because insulin growth factor-1 (IGF-1) has been shown to improve muscle regeneration after injury, and may have a role in muscle preservation following denervation, the purpose of this investigation was to evaluate the histological, immunohistochemical, and electrophysiological differences between normal, denervated, and IGF-1-injected denervated muscle over an 8-week period. Denervated mice gastrocnemius muscles demonstrated a decrease in muscle weight, a decrease in myofiber diameter, an absence of muscle regeneration, an early increase in the number of neuromuscular junctions (NMJs), and a decrease in fast-twitch and maximum tetanic strength as compared to normal muscle up to 8 weeks following denervation. IGF-1-injected denervated muscle, on the other hand, sustained muscle diameter and muscle weight, maintained a smaller number of NMJs, and relatively sustained fast-twitch and maximum tetanic strength as compared to normal muscle over 8 weeks. These data suggest that IGF-1 may help prevent muscle atrophy and secondary functional compromise after denervation.
Day
Charles S
CS
Department of Orthopaedics, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Buranapanitkit
Boonsin
B
Riano
Felix A
FA
Tomaino
Matthew M
MM
Somogyi
George
G
Sotereanos
Dean G
DG
Kuroda
Ryosuke
R
Huard
Johnny
J
D000818:Animals; D003893:Desmin / Q000378:metabolism; D004195:Disease Models, Animal; D007211:Indoles / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D051379:Mice; D009119:Muscle Contraction; D009121:Muscle Denervation / Q000009:adverse effects*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D011950:Receptors, Cholinergic / Q000378:metabolism; D012038:Regeneration; D013997:Time Factors
D003893:Desmin; D007211:Indoles; D011950:Receptors, Cholinergic; C007293:DAPI; D007334:Insulin-Like Growth Factor I