IGF-I and insulin regulate eIF4F formation by different mechanisms in muscle and liver in the ovine fetus

Weihua Shen, Daniel Mallon, David W. Boyle, Edward A. Liechty

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

The mechanisms by which insulin-like growth factor I (IGF-I) and insulin regulate eukaryotic initiation factor (eIF)4F formation were examined in the ovine fetus. Insulin infusion increased phosphorylation of eIF4E-binding protein (4E-BP1) in muscle and liver. IGF-I infusion did not alter 4E-BP1 phosphorylation in liver. In muscle, IGF-I increased 4E-BP1 phosphorylation by 27%; the percentage in the γ-form in the IGF-I group was significantly lower than that in the insulin group. In liver, only IGF-I increased eIF4G. Both IGF-I and insulin increased eIF4E·eIF4G binding in muscle, but only insulin decreased the amount of 4E-BP1 associated with eIF4E. In liver, only IGF-I increased eIF4E·eIF4G binding. Insulin increased the phosphorylation of p70 S6 kinase (p70S6k) in both muscle and liver and protein kinase B (PKB/Akt) in muscle, two indicative signal proteins in the phosphatidylinositol (PI) 3-kinase pathway. IGF-I increased PKB/Akt phosphorylation in muscle but had no effect on p70S6k phosphorylation in muscle or liver. We conclude that insulin and IGF-I modulate eIF4F formation; however, the two hormones have different regulatory mechanisms. Insulin increases phosphorylation of 4E-BP1 and eIF4E·eIF4G binding in muscle, whereas IGF-I regulates eIF4F formation by increasing total eIF4G. Insulin, but not IGF-I, decreased 4E-BP1 content associated with eIF4E. Insulin regulates translation initiation via the PI 3-kinase-p70S6k pathway, whereas IGF-I does so mainly via mechanisms independent of the PI 3-kinase-p70S6k pathway.

Original languageEnglish (US)
Pages (from-to)E593-E603
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume283
Issue number3 46-3
DOIs
StatePublished - Sep 1 2002

Keywords

  • Eukaryotic initiation factors
  • Fetus
  • Insulin
  • Insulin-like growth factor I
  • p70 S6 kinase

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

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