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rhIGF‐I/IGFBP‐3 complex, but not free rhIGF‐I, supports muscle protein biosynthesis in rats during semistarvation

2000; Wiley; Volume: 30; Issue: 5 Linguagem: Inglês

10.1046/j.1365-2362.2000.00652.x

1365-2362

Svanberg, Claes Ohlsson, Kimball, Lundholm,

Diet and metabolism studies

Background The aim of this study was to evaluate the effect of insulin like growth factor‐I (rhIGF‐I) in complex with binding protein 3 (IGFBP 3) compared to the effect of free IGF‐I on muscle protein biosynthesis in undernourished animals. Methods Three groups of female Sprague–Dawley rats (200 g) were initially semi‐starved for 3 days and then treated with saline (controls), rhIGF‐I (1 μg g −1 ) or equimolar amounts of rhIGF‐I/rhIGFBP‐3 complex (5 μg g −1 ) i.v. twice daily for 3 days during continuous semistarvation. Protein metabolism in hind limb skeletal muscle was studied by incorporation of L‐[ 14 C‐U]phenylalanine into proteins, western blot determination of translation initiation factors involved in the binding of the 40S ribosomal subunit to mRNA, and quantification of mRNA content for IGF‐I, IGF‐IR and GH‐R. Plasma measurements of insulin, IGF‐I and amino acids were also performed. Results rhIGF‐I/rhIGFBP‐3, but not rhIGF‐I alone, stimulated protein synthesis by 177 ± 26% ( P ≤ 0.05) in semi‐starved rats. This stimulation was associated with dissociation of the 4E‐BP1.eIF‐4E complex, implicating increased binding of the 40S ribosomal subunit to mRNA, and hence increased initiation of protein synthesis in these animals. Muscle content of IGF‐I mRNA was reduced in semi‐starved animals, whereas IGF‐I receptor mRNA was unaltered despite food restriction. Plasma concentration of IGF‐I was 20% ( P ≤ 0.05) higher in rhIGF‐I/rhIGFBP‐3 treated animals as compared to rats treated with saline or free IGF‐I. Plasma concentrations of amino acids were increased in rhIGF‐I/rhIGFBP‐3 treated animals ( P ≤ 0.05 vs. semi‐starved controls). Conclusion rhIGF‐I/rhIGFBP‐3 (SomatoKine) was a significant stimulator of muscle protein synthesis in chronically semi‐starved animals whereas IGF‐I alone failed to increase protein synthesis during the same experimental conditions. This stimulation was because of increased initiation of translation, likely induced by more physiologic concentrations/kinetics of plasma IGF‐I and amino acids following rhIGF‐I/rhIGFBP‐3 treatment, compared to IGF‐I in its free form.