title: Tangeretin stimulates glucose uptake via regulation of AMPK signaling pathways in C2C12 myotubes and improves glucose tolerance in high-fat diet-induced obese mice.
abstract: Although the flavonoid tangeretin (5, 6, 7, 8, 4'-pentamethoxyflavone) is known to possess beneficial health effects, the anti-diabetic effects and the mechanism of action have not been elucidated. Treatment with 100 μM tangeretin significantly increased the uptake of 2-NBDG in C2C12 myotubes. We also found that AMPK and AS160 were markedly phosphorylated by tangeretin treatment. In addition, pretreatment with an AMPK inhibitor significantly abrogated tangeretin-stimulated AS160 phosphorylation, glucose uptake, and Glut4 translocation from the cytosol to the plasma membrane. Furthermore, disruption of AMPK using siRNA transfection prevented the glucose uptake stimulated by tangeretin. We also examined the anti-diabetic properties of tangeretin in mice on HFD. Administration of HFD plus 200 mg/kg of tangeretin significantly altered weight gain, glucose tolerance, total cholesterol levels, and the secretion of adipocytokines, such as adiponectin, leptin, resistin, IL-6, and MCP-1. Moreover, AMPK was activated by 200 mg/kg of tangeretin in mouse muscle tissue, as expected from the cell system. These results suggest that tangeretin exerts anti-diabetic effects in both cell culture and mouse models, and these effects are necessary for activating AMPK.
authors.affiliation: Korea Food Research Institute, Republic of Korea.
authors.forename: Myung Sunny
authors.initials: MS
authors.lastname: Kim
authors.forename: Haeng Jeon
authors.initials: HJ
authors.lastname: Hur
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Kwon
authors.forename: Jin-Taek
authors.initials: JT
authors.lastname: Hwang
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000378:metabolism; D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat; D047309:Flavones / Q000494:pharmacology*; D020690:GTPase-Activating Proteins / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D047495:PPAR gamma / Q000096:biosynthesis; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering; D052243:Resistin / Q000378:metabolism; D047490:Retinoid X Receptor alpha / Q000096:biosynthesis; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004268:DNA-Binding Proteins; D047309:Flavones; C528734:GLUT4 enhancer factor, mouse; D020690:GTPase-Activating Proteins; D015850:Interleukin-6; D020738:Leptin; D047495:PPAR gamma; D034741:RNA, Small Interfering; D052243:Resistin; D047490:Retinoid X Receptor alpha; C505647:Tbc1d4 protein, mouse; D014157:Transcription Factors; D003847:Deoxyglucose; D055372:AMP-Activated Protein Kinases; D009327:4-Chloro-7-nitrobenzofurazan; C059006:tangeretin; D005947:Glucose; C098340:2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose