p-Synephrine stimulates glucose consumption via AMPK in L6 skeletal muscle cells.
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.
Department of Medicine, School of Medicine, Institute of Medical Science, Jeju National University, 690-756 Jeju, Republic of Korea.
Na-Young
NY
Hong
Zhi-Gang
ZG
Cui
Hee-Kyoung
HK
Kang
Dae-Ho
DH
Lee
Young-Ki
YK
Lee
Deok-Bae
DB
Park
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D013578:Synephrine / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D055372:AMP-Activated Protein Kinases; D005947:Glucose; D013578:Synephrine