title: Liver-derived endocrine IGF-I is not critical for activation of skeletal muscle protein synthesis following oral feeding.
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).
  
  
  CONCLUSIONS
  This study demonstrates that re-synthesis of muscle proteins following starvation is not critically dependent on endocrine liver-derived IGF-I.
authors: Department of Surgery Sahlgrenska University Hospital Kir, Metabol lab Bruna Stråket 20, Gothenburg Sweden. britt-marie.iresjo@surgery.gu.se
authors: Britt-Marie
authors: BM
authors: Iresjö
authors: Johan
authors: J
authors: Svensson
authors: Claes
authors: C
authors: Ohlsson
authors: Kent
authors: K
authors: Lundholm
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005248:Feeding Methods; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D015398:Signal Transduction; D013217:Starvation / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D009124:Muscle Proteins; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases
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