title: Acute in vivo elevation of insulin-like growth factor (IGF) binding protein-1 decreases plasma free IGF-I and muscle protein synthesis.
abstract: This study examined whether the acute elevation of IGF-binding protein-1 (IGFBP-1) decreases the plasma free IGF-I concentration and alters in vivo rates of muscle protein synthesis and glucose uptake. The plasma concentration of human IGFBP-1 was increased to approximately 95 ng/ml in conscious catheterized rats infused iv with human IGFBP-1 for 4 h. Infusion of IGFBP-1 also increased the concentration of endogenous (e.g. rat) IGFBP-1 in the blood, and this response was associated with a 2- to 3-fold elevation of IGFBP-1 mRNA in liver and kidney. IGFBP-1 did not significantly alter the plasma concentration of total IGF-I, but decreased circulating free IGF-I levels by about 50%. IGFBP-1 decreased protein synthesis in the predominantly fast-twitch gastrocnemius muscle (20%), and this change resulted from a decreased translational efficiency that was associated with a decreased phosphorylation of S6K1, but not 4E-BP1. Complementary studies demonstrated that IGFBP-1 also decreased the rates of protein synthesis under basal conditions and in response to stimulation by IGF-I when added in vitro to the fast-twitch epitrochlearis muscle. In contrast, IGFBP-1 did not alter in vivo-determined rates of protein synthesis in the slow-twitch soleus muscle, heart, liver, or kidney. The infusion of IGFBP-1 did not significantly alter the plasma glucose or lactate concentration or the whole body rate of glucose production or disposal. The above-mentioned changes were not mediated indirectly by changes in the plasma insulin or corticosterone concentrations, decreased high energy phosphate content in muscle, or hepatoxicity produced by the infused IGFBP-1. These results demonstrate that acute in vivo elevation in IGFBP-1, of the magnitude observed in various catabolic conditions, is capable of selectively decreasing protein synthesis in fast-twitch skeletal muscle and up-regulating the hepatic and renal syntheses of IGFBP-1 per se. Hence, elevations in circulating and tissue levels of IGFBP-1 may be an important mediator for the muscle catabolism observed in various stress conditions.
authors.affiliation: Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA. clang@psu.edu
authors.forename: Charles H
authors.initials: CH
authors.lastname: Lang
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Vary
authors.forename: Robert A
authors.initials: RA
authors.lastname: Frost
mesh_terms: D000818:Animals; D001835:Body Weight; D002241:Carbohydrates / Q000493:pharmacokinetics; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006358:Hot Temperature; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood* / Q000235:genetics / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002241:Carbohydrates; D018970:Insulin-Like Growth Factor Binding Protein 1; D009124:Muscle Proteins; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I