Resveratrol stimulates glucose transport in C2C12 myotubes by activating AMP-activated protein kinase

Abstract

trans-Resveratrol (t-RVT), a naturally occurring polyphenol found in Polygonum cuspidatum, grape, and red wine, has been reported to have antiinflammatory, 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.

The inhibitory effect of resveratrol on leptin secretion from rat adipocytes

“…As glucose catabolism enhances ATP synthesis in adipocytes, resveratrolinduced attenuation of leptin secretion may result from disturbances in glucose transport and ⁄ or metabolism. Data from the literature concerning the effects of resveratrol on glucose transport are sometimes conflicting depending on experimental conditions [41][42][43][44][45]. While in muscle cells resveratrol is reported to be a stimulator of glucose transport [41,44], in 3T3-L1 adipocytes, resveratrol was found to decrease GLUT4 protein levels and glucose uptake [45].…”

Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats

“…Its cardiovascular properties, including inhibition of platelet aggregation and promotion of vasodilation by enhancing the production of NO [19] have also been described [15,20] and recent studies have reported its beneficial effects against ageing and metabolic diseases [21][22][23][24]. Resveratrol has been described as a potent activator of AMPK in several tissues and cell lines, i.e, HepG2 [24], C2C12 myotubes [25] neuronal cell lines and neurons [26].…”

Wine Lees Polyphenols as a Novel Functional Bioactive Compound in the Protection against Oxidative Stress and Hyperlipidemia

“…clear transcription factor (NF)-κB induced by reactive oxy gen species or activators of protein kinases, and are described as cancer chemoprevention substances, antioxidants, anti-infl ammatory agents, and substances that improve glucose/lipid metabolism or prevent cardiovascular disease (CVD) (6)(7)(8)(9).…”