Elevated IGF-II mRNA and phosphorylation of 4E-BP1 and p70(S6k) in muscle showing clenbuterol-induced anabolism

Alan Arthur Sneddon, Margaret Inkster Delday, John Steven, Charlotte Maltin

Research output: Contribution to journalArticle

Abstract

Muscle wasting affects large numbers of people, but few therapeutic approaches exist to treat and/or reverse this condition. The beta (2)-adrenoceptor agonist clenbuterol produces a muscle-specific protein anabolism in both: normal: and catabolic muscle and has been used to limit muscle wasting in, humans. Because clenbuterol appears to interact with or mimic innervation, its effect on the expression of the neuro trophic agents insulin-like growth factor, (IGF)-II and H19 and their putative pathways was examined in normal rat plantaris muscle. The results showed, that the well-documented early effects of clenbuterol on protein metabolism were preceded by elevated levels of IGF-II and H19 transcripts together with increased phosphorylation of eukaryotic initiation factor (eIF)4E binding protein-1 (4E-BP1) and p70(S6k). By 3 days, transcript levels for IGF-II and H19 and 4E-BP1 and p70(S6k) phosphorylation had returned to control values. These novel findings indicate that clenbuterol-induced muscle anabolism is potentially mediated, at least in part, by an IGF-II-induced activation of 4E-BP1 and p70(S6k).

Original languageEnglish
Pages (from-to)676-682
Number of pages7
JournalAmerican Journal of Physiology: Endocrinology and Metabolism
Volume281
Issue number4
Publication statusPublished - Oct 2001

Keywords

  • hypertrophy
  • beta-agonist
  • growth factor
  • protein translation
  • insulin-like growth factor II
  • eukaryotic initiation factor 4E binding protein-1
  • BETA-ADRENOCEPTOR AGONIST
  • GROWTH FACTOR-II
  • P70 S6 KINASE
  • PROTEIN-SYNTHESIS
  • SKELETAL-MUSCLE
  • GENE-EXPRESSION
  • MESSENGER-RNA
  • RAT MUSCLE
  • INSULIN
  • TISSUES

Cite this

@article{85a3f4f276bc442e95b1deeb315d1d1c,
title = "Elevated IGF-II mRNA and phosphorylation of 4E-BP1 and p70(S6k) in muscle showing clenbuterol-induced anabolism",
abstract = "Muscle wasting affects large numbers of people, but few therapeutic approaches exist to treat and/or reverse this condition. The beta (2)-adrenoceptor agonist clenbuterol produces a muscle-specific protein anabolism in both: normal: and catabolic muscle and has been used to limit muscle wasting in, humans. Because clenbuterol appears to interact with or mimic innervation, its effect on the expression of the neuro trophic agents insulin-like growth factor, (IGF)-II and H19 and their putative pathways was examined in normal rat plantaris muscle. The results showed, that the well-documented early effects of clenbuterol on protein metabolism were preceded by elevated levels of IGF-II and H19 transcripts together with increased phosphorylation of eukaryotic initiation factor (eIF)4E binding protein-1 (4E-BP1) and p70(S6k). By 3 days, transcript levels for IGF-II and H19 and 4E-BP1 and p70(S6k) phosphorylation had returned to control values. These novel findings indicate that clenbuterol-induced muscle anabolism is potentially mediated, at least in part, by an IGF-II-induced activation of 4E-BP1 and p70(S6k).",
keywords = "hypertrophy, beta-agonist, growth factor, protein translation, insulin-like growth factor II, eukaryotic initiation factor 4E binding protein-1, BETA-ADRENOCEPTOR AGONIST, GROWTH FACTOR-II, P70 S6 KINASE, PROTEIN-SYNTHESIS, SKELETAL-MUSCLE, GENE-EXPRESSION, MESSENGER-RNA, RAT MUSCLE, INSULIN, TISSUES",
author = "Sneddon, {Alan Arthur} and Delday, {Margaret Inkster} and John Steven and Charlotte Maltin",
year = "2001",
month = "10",
language = "English",
volume = "281",
pages = "676--682",
journal = "American Journal of Physiology: Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "4",

}

TY - JOUR

T1 - Elevated IGF-II mRNA and phosphorylation of 4E-BP1 and p70(S6k) in muscle showing clenbuterol-induced anabolism

AU - Sneddon, Alan Arthur

AU - Delday, Margaret Inkster

AU - Steven, John

AU - Maltin, Charlotte

PY - 2001/10

Y1 - 2001/10

N2 - Muscle wasting affects large numbers of people, but few therapeutic approaches exist to treat and/or reverse this condition. The beta (2)-adrenoceptor agonist clenbuterol produces a muscle-specific protein anabolism in both: normal: and catabolic muscle and has been used to limit muscle wasting in, humans. Because clenbuterol appears to interact with or mimic innervation, its effect on the expression of the neuro trophic agents insulin-like growth factor, (IGF)-II and H19 and their putative pathways was examined in normal rat plantaris muscle. The results showed, that the well-documented early effects of clenbuterol on protein metabolism were preceded by elevated levels of IGF-II and H19 transcripts together with increased phosphorylation of eukaryotic initiation factor (eIF)4E binding protein-1 (4E-BP1) and p70(S6k). By 3 days, transcript levels for IGF-II and H19 and 4E-BP1 and p70(S6k) phosphorylation had returned to control values. These novel findings indicate that clenbuterol-induced muscle anabolism is potentially mediated, at least in part, by an IGF-II-induced activation of 4E-BP1 and p70(S6k).

AB - Muscle wasting affects large numbers of people, but few therapeutic approaches exist to treat and/or reverse this condition. The beta (2)-adrenoceptor agonist clenbuterol produces a muscle-specific protein anabolism in both: normal: and catabolic muscle and has been used to limit muscle wasting in, humans. Because clenbuterol appears to interact with or mimic innervation, its effect on the expression of the neuro trophic agents insulin-like growth factor, (IGF)-II and H19 and their putative pathways was examined in normal rat plantaris muscle. The results showed, that the well-documented early effects of clenbuterol on protein metabolism were preceded by elevated levels of IGF-II and H19 transcripts together with increased phosphorylation of eukaryotic initiation factor (eIF)4E binding protein-1 (4E-BP1) and p70(S6k). By 3 days, transcript levels for IGF-II and H19 and 4E-BP1 and p70(S6k) phosphorylation had returned to control values. These novel findings indicate that clenbuterol-induced muscle anabolism is potentially mediated, at least in part, by an IGF-II-induced activation of 4E-BP1 and p70(S6k).

KW - hypertrophy

KW - beta-agonist

KW - growth factor

KW - protein translation

KW - insulin-like growth factor II

KW - eukaryotic initiation factor 4E binding protein-1

KW - BETA-ADRENOCEPTOR AGONIST

KW - GROWTH FACTOR-II

KW - P70 S6 KINASE

KW - PROTEIN-SYNTHESIS

KW - SKELETAL-MUSCLE

KW - GENE-EXPRESSION

KW - MESSENGER-RNA

KW - RAT MUSCLE

KW - INSULIN

KW - TISSUES

M3 - Article

VL - 281

SP - 676

EP - 682

JO - American Journal of Physiology: Endocrinology and Metabolism

JF - American Journal of Physiology: Endocrinology and Metabolism

SN - 0193-1849

IS - 4

ER -