title: Insulin-like growth factor 1 stimulates protein synthesis and inhibits protein breakdown in muscle from burned rats.
abstract: BACKGROUND
  Burn injury is associated with substantial whole-body protein loss, reflecting mainly a catabolic response in skeletal muscle. Recent studies suggest that treatment with insulin-like growth factor 1 (IGF-1) may reverse the catabolic response to burn injury, but the effects of IGF-1 on muscle protein synthesis and breakdown rates after burn injury are not known. We tested the hypothesis that IGF-1 blunts the catabolic response in skeletal muscle after burn injury by stimulating protein synthesis and inhibiting protein breakdown and that this effect of IGF-1 is caused by a direct effect on muscle tissue.
  
  
  METHODS
  Intact extensor digitorum longus muscles from burned, sham-burned, and untreated rats were incubated in the absence or presence of different concentrations of IGF-1. Total and myofibrillar protein breakdown rates were measured as net release of tyrosine and 3-methylhistidine, respectively. Protein synthesis rates were determined by measuring the incorporation of (U-14C)-phenylalanine into protein.
  
  
  RESULTS
  IGF-1 stimulated protein synthesis and inhibited protein breakdown in a dose-dependent fashion in muscles from burned and unburned rats. The maximal effect of IGF-1 on protein synthesis was seen at a hormone concentration of 100 ng/mL, whereas protein breakdown was further inhibited when the hormone concentration was increased to 1 microgram/mL. Ubiquitin messenger RNA (mRNA) levels were reduced by IGF-1 in incubated muscles, suggesting that IGF-1 may inhibit ubiquitin-dependent protein breakdown.
  
  
  CONCLUSIONS
  These results suggest that the anabolic effects of IGF-1 after burn may reflect inhibited protein breakdown and stimulated protein synthesis in skeletal muscle and that this response may be caused by a direct effect of IGF-1 on muscle tissue.
authors.affiliation: Department of Surgery, University of Cincinnati, Ohio, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Fang
authors.forename: B G
authors.initials: BG
authors.lastname: Li
authors.forename: J J
authors.initials: JJ
authors.lastname: Wang
authors.forename: J E
authors.initials: JE
authors.lastname: Fischer
authors.forename: P O
authors.initials: PO
authors.lastname: Hasselgren
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002056:Burns / Q000378:metabolism*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014443:Tyrosine / Q000187:drug effects / Q000378:metabolism; D014452:Ubiquitins / Q000032:analysis / Q000187:drug effects / Q000235:genetics
chemical_list: D011506:Proteins; D012333:RNA, Messenger; D014452:Ubiquitins; D014443:Tyrosine; D007334:Insulin-Like Growth Factor I