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.