p-Synephrine stimulates glucose consumption via AMPK in L6 skeletal muscle cells

Biochem Biophys Res Commun. 2012 Feb 24;418(4):720-4. doi: 10.1016/j.bbrc.2012.01.085. Epub 2012 Jan 28.


Interest in p-synephrine, the primary protoalkaloid in the extract of bitter orange and other citrus species, has increased due to its various pharmacological effects and related adverse effects. The lipolytic activity of p-synephrine has been repeatedly revealed by in vitro and in vivo studies and p-synephrine is currently marketed as a dietary supplement for weight loss. The present study investigated the effect of p-synephrine on glucose consumption and its action mechanism in L6 skeletal muscle cells. Treatment of L6 skeletal muscle cells with p-synephrine (0-100μM) did not affect cell viability and increased basal glucose consumption up to 50% over the control in a dose-dependent manner. The basal- or insulin-stimulated lactic acid production as well as glucose consumption was significantly increased by the addition of p-synephrine. p-Synephrine stimulated the phosphorylation of AMPK but not of Akt. p-Synephrine-induced glucose consumption was sensitive to the inhibition of AMPK but not to the inhibition of PI3 kinase. p-Synephrine also stimulated the translocation of Glut4 from the cytoplasm to the plasma membrane; this stimulation was suppressed by the inhibition of AMPK, but not of PI3 kinase. Taken together, p-synephrine can stimulate glucose consumption (Glut4-dependent glucose uptake) by stimulating AMPK activity, regardless of insulin-stimulated PI3 kinase-Akt activity in L6 skeletal muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Adrenergic alpha-Agonists / pharmacology*
  • Animals
  • Cell Line
  • Glucose / metabolism*
  • Humans
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / enzymology
  • Rats
  • Synephrine / pharmacology*


  • Adrenergic alpha-Agonists
  • AMP-Activated Protein Kinases
  • Glucose
  • Synephrine