title: Modulation of cellular glucose metabolism in human HepG2 cells by combinations of structurally related flavonoids.
abstract: METHODS
  Insulin-regulated glucose metabolism in cells is critical for proper metabolic functioning, and insulin resistance leads to type 2 diabetes. We performed a human study to assess the availability of structurally related dietary flavonols and tested their ability to affect cellular glucose uptake, metabolism, and glucose transporter gene expression in a liver HepG2 cell model.
  
  
  RESULTS
  Eight healthy volunteers consumed a meal containing galangin, kaempferol, quercetin, and myricetin. In plasma, myricetin was absent, but the others were present, mostly as conjugates. In HepG2 cells, a combination of galangin, kaempferol, and quercetin (5 μM each) for 12 h increased the acute uptake of [U-(14)C]-glucose and 2-[U-(14)C]-deoxyglucose by almost 100 and ∼10%, respectively. All of the combinations increased glucose metabolism, but the effect on transport was less pronounced and mixed. A mixture of all flavonols significantly increased mRNA expression of the main glucose transporter Glut1 in HepG2 cells.
  
  
  CONCLUSIONS
  These results for the first time show the presence of galangin conjugates in human plasma, and allow direct comparison between absorption of flavonols. A combination of flavonols has the potential to modulate sugar metabolism, both uptake into cells as evident from effects on deoxyglucose, and also further cellular glucose metabolism.
authors.affiliation: School of Food Science and Nutrition, Faculty of Mathematics and Physical Sciences, University of Leeds, Leeds, UK.
authors.forename: Asimina
authors.initials: A
authors.lastname: Kerimi
authors.forename: Fadhilah
authors.initials: F
authors.lastname: Jailani
authors.forename: Gary
authors.initials: G
authors.lastname: Williamson
mesh_terms: D000328:Adult; D005419:Flavonoids / Q000008:administration & dosage; D044948:Flavonols / Q000008:administration & dosage* / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D051272:Glucose Transporter Type 1 / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D044949:Kaempferols / Q000008:administration & dosage; D011794:Quercetin / Q000008:administration & dosage; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D005419:Flavonoids; D044948:Flavonols; D051246:Glucose Transport Proteins, Facilitative; D051272:Glucose Transporter Type 1; D044949:Kaempferols; D012333:RNA, Messenger; C495677:SLC2A1 protein, human; C411811:SLC2A9 protein, human; C037032:galangin; C006552:kaempferol; D011794:Quercetin; D005947:Glucose