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

• Published in: American journal of physiology: endocrinology and metabolism Vol. 283; no. 3; pp. E593 - E603
• Main Authors: Shen, Weihua, Mallon, Daniel, Boyle, David W, Liechty, Edward A
• Format: Journal Article
• Language: English
• Published: United States 01.09.2002
• Subjects: Animals; Blood Glucose - analysis; Carrier Proteins - metabolism; Eukaryotic Initiation Factor-4E; Eukaryotic Initiation Factor-4F; Eukaryotic Initiation Factor-4G; Fetal Blood; Fetus - metabolism; Insulin - physiology; Insulin-Like Growth Factor I - analysis; Insulin-Like Growth Factor I - physiology; Leucine - blood; Liver - embryology; Muscle, Skeletal - embryology; Peptide Initiation Factors - biosynthesis; Peptide Initiation Factors - metabolism; Phosphoproteins - metabolism; Phosphorylation; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Ribosomal Protein S6 Kinases - metabolism; Sheep - embryology
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00570.2001

Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202 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 -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 (p70 S6k ) 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 p70 S6k 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-p70 S6k pathway, whereas IGF-I does so mainly via mechanisms independent of the PI 3-kinase-p70 S6k pathway. insulin; insulin-like growth factor I; fetus; eukaryotic initiation factors; p70 S6 kinase