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.
1-phosphatidylinositol 3-kinase; 5′-AMP-activated protein kinase; Acetyl-CoA carboxylase; Glucose; Proto-oncogene proteins c-akt; Resveratrol
EMTREE drug terms: hydroxymethylglutaryl coenzyme A reductase kinase; insulin; phosphatidylinositol 3 kinase; resveratrol
EMTREE medical terms: animal cell; article; concentration response; controlled study; drug potentiation; enzyme activation; glucose transport; lipid metabolism; metabolic syndrome X; mouse; myotube; non insulin dependent diabetes mellitus; nonhuman; signal transduction
MeSH: 1-Phosphatidylinositol 3-Kinase; Animals; Biological Transport; Cell Line; Enzyme Activation; Glucose; Insulin; Mice; Models, Biological; Multienzyme Complexes; Muscle Fibers; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Stilbenes
Medline is the source for the MeSH terms of this document.
Species Index: Polygonum cuspidatum; Vitaceae
Chemicals and CAS Registry Numbers: hydroxymethylglutaryl coenzyme A reductase kinase, 172522-01-9, 72060-32-3; insulin, 9004-10-8; phosphatidylinositol 3 kinase, 115926-52-8; resveratrol, 501-36-0;1-Phosphatidylinositol 3-Kinase, EC 22.214.171.124; 5'-AMP-activated protein kinase, EC 126.96.36.199; Glucose, 50-99-7; Insulin, 11061-68-0; Multienzyme Complexes; Protein-Serine-Threonine Kinases, EC 188.8.131.52; Proto-Oncogene Proteins c-akt, EC 184.108.40.206; resveratrol, 501-36-0; Stilbenes
Manufacturers:Drug manufacturer: Sigma.