title: Effect of insulin-like growth factor I in murine muscular dystrophy.
abstract: 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.
authors.affiliation: Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, New York 11030, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Zdanowicz
authors.forename: J
authors.initials: J
authors.lastname: Moyse
authors.forename: M A
authors.initials: MA
authors.lastname: Wingertzahn
authors.forename: M
authors.initials: M
authors.lastname: O'Connor
authors.forename: S
authors.initials: S
authors.lastname: Teichberg
authors.forename: A E
authors.initials: AE
authors.lastname: Slonim
mesh_terms: 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
chemical_list: D004044:Dietary Proteins; D008762:Methylhistidines; D009124:Muscle Proteins; D011994:Recombinant Proteins; D014443:Tyrosine; D007334:Insulin-Like Growth Factor I; C028118:3-methylhistidine