Stimulation of muscle cell glucose uptake by resveratrol through sirtuins and AMPK.
Although recent studies in vitro and in vivo indicate that the polyphenol resveratrol (RSV) has anti-diabetic properties, the exact mechanisms involved are not known. In the present study, we examined the effects of RSV and the mechanism of regulation of glucose uptake in skeletal muscle cells. In L6 myotubes RSV (100 microM) induced maximum stimulation of glucose (2DG) uptake (201+/-8.90% of control, p<0.001), an effect that was similar to insulin action. RSV-stimulated glucose uptake was abolished by AMPK inhibition. In the presence of the sirtuin inhibitor nicotinamide, RSV-stimulated 2DG uptake and AMPK phosphorylation were abolished. RSV did not stimulate significant translocation of GLUT4 or GLUT1 transporters. However, treatment with indinavir, a GLUT4 specific inhibitor, blocked RSV-stimulated glucose uptake. We propose that RSV elevates glucose uptake in muscle cells through a mechanism that involves sirtuins and AMPK and possibly stimulation of GLUT4 transporter intrinsic activity.
Breen
Danna M
DM
Faculty of Applied Health Sciences, Brock University, St. Catharines, Ont., Canada L2S 3A1.
Sanli
Toran
T
Giacca
Adria
A
Tsiani
Evangelia
E
D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D019469:Indinavir / Q000494:pharmacology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D000077185:Resveratrol; D037761:Sirtuins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*
D000975:Antioxidants; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; C495679:Slc2a1 protein, rat; C495694:Slc2a4 protein, rat; D013267:Stilbenes; D009536:Niacinamide; D019469:Indinavir; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D037761:Sirtuins; D005947:Glucose; D000077185:Resveratrol