Resveratrol stimulates glucose transport in C2C12 myotubes by activating AMP-activated protein kinase.
trans-Resveratrol (t-RVT), a naturally occurring polyphenol found in Polygonum cuspidatum, grape, and red wine, has been reported to have anti-inflammatory, cardioprotective, and cancer chemopreventive properties. However antidiabetic effect of t-RVT has not yet been reported. In this study, we show that t-RVT increases glucose uptake in C2C12 myotubes by activating AMP-activated protein kinase (AMPK), uncovering an antidiabetic potential of t-RVT for the first time. AMPK plays a central role in the regulation of glucose and lipid metabolism, and hence it is considered a novel therapeutic target for metabolic syndrome such as type 2 diabetes. t-RVT significantly induced glucose uptake in C2C12 cells, via AMPK activation, but not a phosphatidylinositol-3 kinase (PI-3 kinase) signal pathway. The induced glucose uptake was attenuated by pretreatment with a pharmacological inhibitor for AMPK, indicating that the effect of t-RVT primarily depends on AMPK activation. However, in the presence of insulin, t-RVT also potentiated the effect of insulin on glucose uptake via AMPK activation, which led to further activation of PI-3 kinase/Akt signal pathway.
Park
Chang Eun
CE
Department of East-West Medicine, Graduate School, Kyung Hee University, Seoul 130-701, Korea.
Kim
Min-Jung
MJ
Lee
Jong Hwa
JH
Min
Byung-Il
BI
Bae
Hyunsu
H
Choe
Wonchae
W
Kim
Sung-Soo
SS
Ha
Joohun
J
D055372:AMP-Activated Protein Kinases; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D055372:AMP-Activated Protein Kinases; D005947:Glucose; D007328:Insulin; D009097:Multienzyme Complexes; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000077185:Resveratrol; D013267:Stilbenes