IGF-I/IGFBP-3 binary complex modulates sepsis-induced inhibition of protein synthesis in skeletal muscle.
The present study evaluated the ability of insulin-like growth factor I (IGF-I) complexed with IGF binding protein-3 (IGFBP-3) to modulate the sepsis-induced inhibition of protein synthesis in gastrocnemius. Beginning 16 h after the induction of sepsis, either the binary complex or saline was injected twice daily via a tail vein, with measurements made 3 and 5 days later. By day 3, sepsis had reduced plasma IGF-I concentrations approximately 50% in saline-treated rats. Administration of the binary complex provided exogenous IGF-I to compensate for the sepsis-induced diminished plasma IGF-I. Sepsis decreased rates of protein synthesis in gastrocnemius relative to controls by limiting translational efficiency. Treatment of septic rats with the binary complex for 5 days attenuated the sepsis-induced inhibition of protein synthesis and restored translational efficiency to control values. Assessment of potential mechanisms regulating translational efficiency showed that neither the sepsis-induced change in gastrocnemius content of eukaryotic initiation factor 2B (eIF2B), the amount of eIF4E associated with 4E binding protein-1 (4E-BP1), nor the phosphorylation state of 4E-BP1 or eIF4E were altered by the binary complex. Overall, the results are consistent with the hypothesis that decreases in plasma IGF-I are partially responsible for enhanced muscle catabolism during sepsis.
Svanberg
E
E
Department of Surgery, Gotenburg University, S-41345 Gotenburg, Sweden.
Frost
R A
RA
Lang
C H
CH
Isgaard
J
J
Jefferson
L S
LS
Kimball
S R
SR
Vary
T C
TC
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins; D020717:Eukaryotic Initiation Factor-2B / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E; D007328:Insulin / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism* / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000378:metabolism; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D009929:Organ Size; D010448:Peptide Initiation Factors / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000235:genetics; D011986:Receptors, Somatotropin / Q000235:genetics; D018805:Sepsis / Q000378:metabolism*
D001786:Blood Glucose; D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D020717:Eukaryotic Initiation Factor-2B; D039561:Eukaryotic Initiation Factor-4E; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D010448:Peptide Initiation Factors; D010750:Phosphoproteins; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1