Leucine modulates dynamic phosphorylation events in insulin signaling pathway and enhances insulin-dependent glycogen synthesis in human skeletal muscle cells

Barbara Di Camillo, Federica Eduati, Sreekumaran K. Nair, Angelo Avogaro, Gianna M. Toffolo

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Background: Branched-chain amino acids, especially leucine, are known to interact with insulin signaling pathway and glucose metabolism. However, the mechanism by which this is exerted, remain to be clearly defined. In order to examine the effect of leucine on muscle insulin signaling, a set of experiments was carried out to quantitate phosphorylation events along the insulin signaling pathway in human skeletal muscle cell cultures. Cells were exposed to insulin, leucine or both, and phosphorylation events of key insulin signaling molecules were tracked over time so as to monitor time-related responses that characterize the signaling events and could be missed by a single sampling strategy limited to pre/post stimulus events. Results: Leucine is shown to increase the magnitude of insulin-dependent phosphorylation of protein kinase B (AKT) at Ser473 and glycogen synthase kinase (GSK3β) at Ser21-9. Glycogen synthesis follows the same pattern of GSK3β, with a significant increase at 100 μM leucine plus insulin stimulus. Moreover, data do not show any statistically significant increase of pGSK3β and glycogen synthesis at higher leucine concentrations. Leucine is also shown to increase the magnitude of insulin-mediated extracellularly regulated kinase (ERK) phosphorylation; however, differently from AKT and GSK3β, ERK shows a transient behavior, with an early peak response, followed by a return to the baseline condition. Conclusions: These experiments demonstrate a complementary effect of leucine on insulin signaling in a human skeletal muscle cell culture, promoting insulin-activated GSK3β phosphorylation and glycogen synthesis.

Original languageEnglish (US)
Article number9
JournalBMC Cell Biology
Volume15
Issue number1
DOIs
StatePublished - Mar 20 2014

ASJC Scopus subject areas

  • Cell Biology

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