Insulin and IGF-I stimulate the formation of the eukaryotic initiation factor 4F complex and protein synthesis in C2C12 myotubes independent of availability of external amino acids

Wei Hua Shen, David Boyle, Paul Wisniowski, Aashia Bade, Edward A. Liechty

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Abstract

The objective of this study was to investigate the effect of insulin and IGF-I on protein synthesis and translation initiation in C2C12 myotubes in nutrient-deprived Dulbecco's phosphate buffered saline (DPBS). The results showed that insulin and IGF-I increased protein synthesis by 62% and 35% respectively in DPBS, and the effect was not affected by rapamycin, but was blocked by LY294002. Insulin and IGF-I stimulated eukaryotic initiation factor 4E (eIF4E) binding protein (4EBP1) phosphorylation in a dose-dependent manner, and the stimulation was independent of availability of external amino acids. Both LY294002 and rapamycin blocked the insulin and IGF-I-induced increases in 4EBP1 phosphorylation. The results also showed that insulin and IGF-I were able to stimulate PKB/Akt phosphorylation, glycogen synthase kinase (GSK) 3β phosphorylation and mTOR phosphorylation in DPBS. Insulin and IGF-I increased the amount of eIF4G associated with eIF4E in nutrient-deprived C2C12 myotubes. The amount of 4EBP1 associated with eIF4E was decreased after insulin or IGF-I stimulation. We conclude that in C2C12 myotubes, insulin and IGF-I may regulate protein synthesis and translation initiation independent of external amino acid supply via the phosphatidylinositol-3 kinase-PKB/Akt-mTOR pathway.

Original languageEnglish
Pages (from-to)275-289
Number of pages15
JournalJournal of Endocrinology
Volume185
Issue number2
DOIs
StatePublished - May 2005

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Eukaryotic Initiation Factor-4F
Skeletal Muscle Fibers
Insulin-Like Growth Factor I
Insulin
Amino Acids
Eukaryotic Initiation Factor-4E
Phosphorylation
Proteins
Translational Peptide Chain Initiation
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Phosphates
Sirolimus
Phosphatidylinositol 3-Kinase
Glycogen Synthase Kinase 3
Food
Carrier Proteins

ASJC Scopus subject areas

  • Endocrinology

Cite this

Insulin and IGF-I stimulate the formation of the eukaryotic initiation factor 4F complex and protein synthesis in C2C12 myotubes independent of availability of external amino acids. / Shen, Wei Hua; Boyle, David; Wisniowski, Paul; Bade, Aashia; Liechty, Edward A.

In: Journal of Endocrinology, Vol. 185, No. 2, 05.2005, p. 275-289.

Research output: Contribution to journalArticle

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