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

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

Research output: Contribution to journalArticle

26 Citations (Scopus)

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
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume283
Issue number3 46-3
StatePublished - Sep 1 2002

Fingerprint

Insulin-Like Growth Factor I
Liver
Muscle
Sheep
Fetus
Phosphorylation
Insulin
Muscles
70-kDa Ribosomal Protein S6 Kinases
Phosphatidylinositol 3-Kinase
Eukaryotic Initiation Factor-4F
Proto-Oncogene Proteins c-akt
Muscle Proteins
Carrier Proteins
Hormones

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

IGF-I and insulin regulate eIF4F formation by different mechanisms in muscle and liver in the ovine fetus. / Shen, Weihua; Mallon, Daniel; Boyle, David; Liechty, Edward A.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 283, No. 3 46-3, 01.09.2002.

Research output: Contribution to journalArticle

@article{737b2cf3d3b244ce97c5301d640ec362,
title = "IGF-I and insulin regulate eIF4F formation by different mechanisms in muscle and liver in the ovine fetus",
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.",
keywords = "Eukaryotic initiation factors, Fetus, Insulin, Insulin-like growth factor I, p70 S6 kinase",
author = "Weihua Shen and Daniel Mallon and David Boyle and Liechty, {Edward A.}",
year = "2002",
month = "9",
day = "1",
language = "English",
volume = "283",
journal = "American Journal of Physiology",
issn = "0193-1857",
publisher = "American Physiological Society",
number = "3 46-3",

}

TY - JOUR

T1 - IGF-I and insulin regulate eIF4F formation by different mechanisms in muscle and liver in the ovine fetus

AU - Shen, Weihua

AU - Mallon, Daniel

AU - Boyle, David

AU - Liechty, Edward A.

PY - 2002/9/1

Y1 - 2002/9/1

N2 - 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.

AB - 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.

KW - Eukaryotic initiation factors

KW - Fetus

KW - Insulin

KW - Insulin-like growth factor I

KW - p70 S6 kinase

UR - http://www.scopus.com/inward/record.url?scp=0036710528&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036710528&partnerID=8YFLogxK

M3 - Article

C2 - 12169454

AN - SCOPUS:0036710528

VL - 283

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0193-1857

IS - 3 46-3

ER -