title: IGF-I stimulates protein synthesis but does not inhibit protein breakdown in muscle from septic rats.
abstract: Sepsis is associated with reduced protein synthesis and increased protein degradation in skeletal muscle. We examined the effects of insulin-like growth factor I (IGF-I) on protein synthesis and breakdown in muscles from nonseptic and septic rats. Sepsis was induced by cecal ligation and puncture; control rats were sham operated. Extensor digitorum longus muscles were incubated in the absence or presence of IGF-I at concentrations ranging from 100 ng/ml to 10 micrograms/ml. Total and myofibrillar protein breakdown rates were measured as net release of tyrosine and 3-methylhistidine, respectively. Protein synthesis was determined by measuring incorporation of [U-14C]phenylalanine into protein. IGF-I stimulated protein synthesis in a dose-dependent fashion in muscles from both sham-operated and septic rats, with a maximal effect seen at a hormone concentration between 500 and 1,000 ng/ml. IGF-I inhibited total and myofibrillar protein breakdown in muscles from sham-operated rats, whereas in muscles from septic rats, IGF-I had no effect on protein breakdown, even at high concentrations. The results suggest that protein breakdown in skeletal muscle becomes resistant to IGF-I during sepsis and that this resistance reflects a postreceptor defect.
authors.affiliation: Department of Surgery, University of Cincinnati 45267-0558, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Hobler
authors.forename: A B
authors.initials: AB
authors.lastname: Williams
authors.forename: J E
authors.initials: JE
authors.lastname: Fischer
authors.forename: P O
authors.initials: PO
authors.lastname: Hasselgren
mesh_terms: D000818:Animals; D002432:Cecum / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000494:pharmacology*; D008026:Ligation; D008297:Male; D008762:Methylhistidines / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism; D011677:Punctures; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000209:etiology / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D008762:Methylhistidines; D009124:Muscle Proteins; D014443:Tyrosine; D007334:Insulin-Like Growth Factor I; C028118:3-methylhistidine