title: Naringenin, a citrus flavonoid, increases muscle cell glucose uptake via AMPK.
abstract: Naringenin, a flavonoid found in high concentrations in grapefruit, has been reported to have antioxidant, antiatherogenic, and anticancer effects. Effects on lipid and glucose metabolism have also been reported. Naringenin is structurally similar to the polyphenol resveratrol, that has been reported to activate the SIRT1 protein deacetylase and to have antidiabetic properties. In the present study we examined the direct effects of naringenin on skeletal muscle glucose uptake and investigated the mechanism involved. Naringenin stimulated glucose uptake in L6 myotubes in a dose- and time-dependent manner. Maximum stimulation was seen with 75 microM naringenin for 2 h (192.8+/-24%, p<0.01), a response comparable to maximum insulin response (190.1+/-13%, p<0.001). Similar to insulin, naringenin did not increase glucose uptake in myoblasts indicating that GLUT4 glucose transporters may be involved in the naringenin-stimulated glucose uptake. In addition, naringenin did not have a significant effect on basal or insulin-stimulated Akt phosphorylation while significantly increased AMPK phosphorylation/activation. Furthermore, silencing of AMPK, using siRNA approach, abolished the naringenin-stimulated glucose uptake. The SIRT1 inhibitors nicotinamide and EX527 did not have an effect on naringenin-stimulated AMPK phosphorylation and glucose uptake. Our data show that naringenin increases glucose uptake by skeletal muscle cells in an AMPK-dependent manner.
authors.affiliation: Faculty of Applied Health Sciences, Brock University, St. Catharines, ON, Canada L2S 3A1.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Zygmunt
authors.forename: Brandon
authors.initials: B
authors.lastname: Faubert
authors.forename: Jordan
authors.initials: J
authors.lastname: MacNeil
authors.forename: Evangelia
authors.initials: E
authors.lastname: Tsiani
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D032083:Citrus paradisi / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D044950:Flavanones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D044950:Flavanones; D005419:Flavonoids; D034741:RNA, Small Interfering; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; C005273:naringenin; D005947:Glucose