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

Elisabeth Svanberg, C. Ohlsson, Scot Kimball, K. Lundholm

Research output: Contribution to journalArticle

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Abstract

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[14C-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.

Original languageEnglish (US)
Pages (from-to)438-446
Number of pages9
JournalEuropean Journal of Clinical Investigation
Volume30
Issue number5
DOIs
StatePublished - May 22 2000

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Insulin-Like Growth Factor Binding Protein 3
Muscle Proteins
Biosynthesis
Protein Biosynthesis
Insulin-Like Growth Factor I
Rats
Animals
Messenger RNA
Eukaryotic Small Ribosome Subunits
Plasmas
Proteins
Amino Acids
Muscle
Peptide Initiation Factors
IGF Type 1 Receptor
Phenylalanine
Metabolism
Sprague Dawley Rats
Carrier Proteins
Skeletal Muscle

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry

Cite this

@article{cd46aea9087e413f92a51b573762a95e,
title = "rhIGF-I/IGFBP-3 complex, but not free rhIGF-I, supports muscle protein biosynthesis in rats during semistarvation",
abstract = "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[14C-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.",
author = "Elisabeth Svanberg and C. Ohlsson and Scot Kimball and K. Lundholm",
year = "2000",
month = "5",
day = "22",
doi = "10.1046/j.1365-2362.2000.00652.x",
language = "English (US)",
volume = "30",
pages = "438--446",
journal = "European Journal of Clinical Investigation",
issn = "0014-2972",
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}

rhIGF-I/IGFBP-3 complex, but not free rhIGF-I, supports muscle protein biosynthesis in rats during semistarvation. / Svanberg, Elisabeth; Ohlsson, C.; Kimball, Scot; Lundholm, K.

In: European Journal of Clinical Investigation, Vol. 30, No. 5, 22.05.2000, p. 438-446.

Research output: Contribution to journalArticle

TY - JOUR

T1 - rhIGF-I/IGFBP-3 complex, but not free rhIGF-I, supports muscle protein biosynthesis in rats during semistarvation

AU - Svanberg, Elisabeth

AU - Ohlsson, C.

AU - Kimball, Scot

AU - Lundholm, K.

PY - 2000/5/22

Y1 - 2000/5/22

N2 - 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[14C-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.

AB - 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[14C-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.

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U2 - 10.1046/j.1365-2362.2000.00652.x

DO - 10.1046/j.1365-2362.2000.00652.x

M3 - Article

VL - 30

SP - 438

EP - 446

JO - European Journal of Clinical Investigation

JF - European Journal of Clinical Investigation

SN - 0014-2972

IS - 5

ER -