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Open Access Research article

Liver-derived endocrine IGF-I is not critical for activation of skeletal muscle protein synthesis following oral feeding

Britt-Marie Iresjö1*, Johan Svensson2, Claes Ohlsson2 and Kent Lundholm1

Author Affiliations

1 Department of Surgery Sahlgrenska University Hospital Kir., Metabol lab Bruna Stråket 20-413 45, Gothenburg Sweden

2 Department of Internal Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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BMC Physiology 2013, 13:7  doi:10.1186/1472-6793-13-7

Published: 8 May 2013

Abstract

Background

Insulin-like growth factor-1 (IGF-1) is produced in various tissues to stimulate protein synthesis under different conditions. It is however, difficult to distinguish effects by locally produced IGF-1 compared to liver-derived IGF-1 appearing in the circulation. In the present study the role of liver-derived endocrine IGF-I for activation of skeletal muscle protein synthesis following feeding was evaluated.

Results

Transgenic female mice with selective knockout of the IGF-I gene in hepatocytes were freely fed, starved overnight and subsequently refed for 3 hours and compared to wild types (wt). Liver IGF-I knockout mice had 70% reduced plasma IGF-I. Starvation decreased and refeeding increased muscle protein synthesis (p < 0.01), similarly in both IGF-I knockouts and wt mice. Phosphorylation of p70s6k and mTOR increased and 4EBP1 bound to eIF4E decreased in both IGF-I knockouts and wt mice after refeeding (p < 0.05). Muscle transcripts of IGF-I decreased and IGF-I receptor increased (p < 0.01) in wild types during starvation but similar alterations did not reach significance in knockouts (p>0.05). mTOR mRNA increased in knockouts only during starvation. Plasma glucose decreased during starvation in all groups in parallel to insulin, while plasma IGF-I and GH did not change significantly among the groups during starvation-refeeding. Plasma amino acids declined and increased during starvation-refeeding in wild type mice (p < 0.05), but less so in IGF-I (−/−) knockouts (p < 0.08).

Conclusion

This study demonstrates that re-synthesis of muscle proteins following starvation is not critically dependent on endocrine liver-derived IGF-I.

Keywords:
IGF-I; Muscle protein synthesis; Cell signaling; Amino acid