IGF-I and insulin regulate eIF4F formation by different mechanisms in muscle and liver in the ovine fetus
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 increa...
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Published in | American journal of physiology: endocrinology and metabolism Vol. 283; no. 3; pp. E593 - E603 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.09.2002
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Subjects | |
Online Access | Get full text |
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Summary: | 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 |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0193-1849 1522-1555 |
DOI: | 10.1152/ajpendo.00570.2001 |