title: Cytokines block the effects of insulin-like growth factor-I (IGF-I) on glucose uptake and lactate production in skeletal muscle but do not influence IGF-I-induced changes in protein turnover.
abstract: There is evidence that proinflammatory cytokines are involved in the regulation of muscle protein breakdown in various catabolic conditions but the mechanisms are not fully understood. Previous studies suggest that cytokines reduce circulating and tissue levels of insulin-like growth factor-I (IGF-I) and may block the anabolic effects of the hormone in certain cell types and tissues. We tested the hypothesis that a mixture of tumor necrosis factor alpha, interleukin-1 alpha, and interferon-gamma block the anabolic effects of IGF-I in skeletal muscle. Muscles from burned or unburned rats were incubated in the absence or presence of 1 microgram/mL of IGF-I with or without the addition of the cytokines. As expected, IGF-I stimulated protein synthesis and inhibited protein breakdown in incubated muscles. The cytokines did not influence protein turnover rates in muscles incubated with or without IGF-I. In additional experiments, the effects of IGF-I on glucose uptake and lactate production were tested. IGF-I increased glucose uptake approximately 2.5-fold and stimulated lactate production approximately 5-fold. These effects of the hormone were significantly inhibited by the cytokine mixture. The results suggest that cytokines do not induce protein catabolism by directly inhibiting the anabolic effects of IGF-I in muscle tissue. The inhibitory effects of the cytokines on IGF-I-stimulated glucose transport and lactate production suggest that the lack of effect of cytokines on protein metabolism was not due to a metabolic unresponsiveness of the incubated muscles to the cytokines.
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 H
authors.initials: JH
authors.lastname: James
authors.forename: J E
authors.initials: JE
authors.lastname: Fischer
authors.forename: P O
authors.initials: PO
authors.lastname: Hasselgren
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002056:Burns / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D009124:Muscle Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; D007334:Insulin-Like Growth Factor I; D007371:Interferon-gamma; D005947:Glucose