Effect of insulin-like growth factor I in murine muscular dystrophy.
In muscular dystrophy there is an imbalance between muscle protein synthesis and protein degradation, resulting in net muscle catabolism and progressive muscle weakness and wasting. Both insulin and insulin-like growth factor I (IGF-I) are known to have an anabolic effect on skeletal muscle, which is believed to be enhanced in the presence of elevated concentrations of amino acids. We examined the effects of 4-week administration of recombinant human IGF-I (rhIGF-I), both alone and supplemented with a high protein diet (HPD), on muscle metabolism, morphology, and function in the 129 ReJ dystrophic mouse. rhIGF-I significantly reduced muscle protein degradation (P < 0.001), increased muscle protein content (P < 0.05), decreased fiber area variability (P < 0.01), and increased hind limb utilization (P < 0.01). Supplementation of rhIGF-I therapy with a HPD resulted in a significant increase in muscle protein synthesis (P < 0.05) in addition to a further increase in the above parameters. We conclude that rhIGF-I causes an improvement in muscle metabolism, morphology, and function in dystrophic mice, and this effect is further enhanced by the presence of a HPD.
Zdanowicz
M M
MM
Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, New York 11030, USA.
Moyse
J
J
Wingertzahn
M A
MA
O'Connor
M
M
Teichberg
S
S
Slonim
A E
AE
D000818:Animals; D004044:Dietary Proteins / Q000008:administration & dosage; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000627:therapeutic use; D007700:Kinetics; D008297:Male; D008762:Methylhistidines / Q000652:urine; D051379:Mice; D009124:Muscle Proteins / Q000096:biosynthesis / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D014443:Tyrosine / Q000378:metabolism
D004044:Dietary Proteins; D008762:Methylhistidines; D009124:Muscle Proteins; D011994:Recombinant Proteins; D014443:Tyrosine; D007334:Insulin-Like Growth Factor I; C028118:3-methylhistidine