Post-transcriptional gene silencing of ribosomal protein S6 kinase 1 restores insulin action in leucine-treated skeletal muscle

A. Deshmukh, F. Salehzadeh, S. Metayer-Coustard, R. Fahlman, K. S. Nair, L. Al-Khalili

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Excessive nutrients, especially amino acids, impair insulin action on glucose metabolism in skeletal muscle. We tested the hypothesis that the branched-chain amino acid leucine reduces acute insulin action in primary myotubes via a negative feedback mechanism involving ribosomal protein S6 kinase 1 (S6K1). The effect of S6K1 on glucose metabolism was determined by applying RNA interference (siRNA). Leucine (5 mM) reduced glucose uptake and incorporation to glycogen by 13% and 22%, respectively, compared to the scramble siRNA-transfected control at the basal level. Leucine also reduced insulin-stimulated Akt phosphorylation, glucose uptake and glucose incorporation to glycogen (39%, 39% and 37%, respectively), and this reduction was restored after S6K1 silencing. Depletion of S6K1 enhanced basal glucose utilization and protected against the development of impaired insulin action, in response to excessive leucine. In conclusion, S6K1 plays an important role in the regulation of insulin action on glucose metabolism in skeletal muscle.

Original languageEnglish (US)
Pages (from-to)1457-1466
Number of pages10
JournalCellular and Molecular Life Sciences
Volume66
Issue number8
DOIs
StatePublished - Apr 1 2009

Keywords

  • Branched chain amino acids
  • Glucose uptake
  • Glycogen synthesis
  • Nutrient sensing
  • Signal transduction

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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