Changes in 4E-BP1 and p70S6K phosphorylation in skeletal muscle of the ovine fetus after prolonged maternal fasting: Effects of insulin and IGF-I

Weihua Shen, David Boyle, Edward A. Liechty

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Abstract

This study was conducted to investigate fasting-induced alterations in insulin signaling to the regulatory components of the translation machinery. Insulin (890 mlU/h) and IGF-I (40 nM/h) were infused into a chronically catheterized ovine fetus (0.85 gestation) for 7 h following a 5-d maternal fast. Amino acid and glucose concentrations were clamped to minimize the effects of alterations in circulating substrate concentrations. The IGF-I induced increase in 4E-BP1 phosphorylation (percentage in the γ form) increased from 28% in control to 44% (NS). The insulin-induced increase in 4E-BP1 phosphorylation was more pronounced, and the γ percentage was 56% on average in the insulin group. The insulin-induced increase in 4E-BP1 phosphorylation was lower than in fed animals and did not result in significant changes in eIF4E-4E-BP1 binding or eIF4E-eIF4G binding. Insulin increased PKB/Akt phosphorylation and p70S6K phosphorylation to a similar extent as in fed animals. We conclude that maternal fasting resulted in reduced insulin sensitivity of 4E-BP1 phosphorylation and eIF4F formation. This reduced insulin-induced 4E-BP1 phosphorylation was not due to a global defect in insulin signaling; the defects underlying the reduced basal phosphorylation and insulin-responsiveness of 4E-BP1 in fasted animals may be in signaling components other than, or downstream of, PKB/Akt. Selective inhibition of downstream components of insulin signaling allows fetuses to adapt to nutritional stress by decreasing the anabolic response to insulin and other growth factors, so that more amino acids can be used as oxidative substrate to compensate for shortage of energy due to reduced glucose supply.

Original languageEnglish
Pages (from-to)833-839
Number of pages7
JournalPediatric Research
Volume58
Issue number5
DOIs
StatePublished - Nov 2005

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70-kDa Ribosomal Protein S6 Kinases
Insulin-Like Growth Factor I
Fasting
Sheep
Skeletal Muscle
Fetus
Phosphorylation
Insulin
Maternal Inheritance
Mothers
Amino Acids
Glucose
Insulin Resistance
Intercellular Signaling Peptides and Proteins

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Changes in 4E-BP1 and p70S6K phosphorylation in skeletal muscle of the ovine fetus after prolonged maternal fasting : Effects of insulin and IGF-I. / Shen, Weihua; Boyle, David; Liechty, Edward A.

In: Pediatric Research, Vol. 58, No. 5, 11.2005, p. 833-839.

Research output: Contribution to journalArticle

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