title: Phenolic compounds isolated from fermented blueberry juice decrease hepatocellular glucose output and enhance muscle glucose uptake in cultured murine and human cells.
abstract: BACKGROUND
  We recently reported that blueberry juice fermented (FJ) with Serratia vaccinii bacterium has antidiabetic activities both in vivo and in vitro. The purpose of this project was to elucidate the effect of FJ on glucose homeostasis in liver and skeletal muscle cells and to identify active fractions/compounds responsible for this effect.
  
  
  METHODS
  FJ was fractionated using standard chromatography procedures. Hepatic (H4IIE, HepG2) and skeletal muscle cells (C2C12) were treated with maximum non-toxic concentrations of FJ, fractions and isolated compounds thereof. Glucose-6-phosphatase (G6Pase) activity was measured using glucose oxidase method. To measure glucose uptake and glycogen synthase (GS) activity, radioactive assays were used.
  
  
  RESULTS
  Fractionation of FJ yielded seven fractions. FJ and its phenolic fractions F2, F3-1 and F3-2 respectively inhibited G-6Pase by 31, 45, 51 and 26%; activated GS by 2.3-, 2.3-, 2.2- and 2-fold; and stimulated glucose uptake by 19, 25, 18 and 15%, as compared to DMSO vehicle control. Subfractionation of the active fractions yielded 4 compounds (catechol, chlorogenic, gallic and protocatechuic acid). Catechol, yielding the greatest bioactivity in G6Pase and glucose uptake assays, decreased G6Pase activity by 54%, increased GS by 2-fold and stimulated glucose uptake by 44% at 45.5 μM.
  
  
  CONCLUSIONS
  This study identifies novel potential antidiabetic compounds that can help standardize FJ.
authors.affiliation: Natural Health Products and Metabolic Diseases Laboratory, Department of Pharmacology and Physiology, Université de Montréal, Station Centre-Ville, P.O. Box 6128, Montréal, Québec, H3C 3J7, Canada.|Canadian Institutes of Health Research Team in Aboriginal Antidiabetic Medicines and Montreal Diabetes Research Center, Montreal, Canada.
authors.forename: Abir
authors.initials: A
authors.lastname: Nachar
authors.affiliation: Natural Health Products and Metabolic Diseases Laboratory, Department of Pharmacology and Physiology, Université de Montréal, Station Centre-Ville, P.O. Box 6128, Montréal, Québec, H3C 3J7, Canada.|Canadian Institutes of Health Research Team in Aboriginal Antidiabetic Medicines and Montreal Diabetes Research Center, Montreal, Canada.|Department of Pharmacognosy, University of Beni-Suef, Beni-Suef, Egypt.
authors.forename: Hoda M
authors.initials: HM
authors.lastname: Eid
authors.affiliation: Food chemistry, Agriculture and Agri-Food Canada, Government of Canada, Kentville, Nova Scotia, Canada.
authors.forename: Melinda
authors.initials: M
authors.lastname: Vinqvist-Tymchuk
authors.affiliation: Department of Nutritional Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Canada.
authors.forename: Tri
authors.initials: T
authors.lastname: Vuong
authors.affiliation: Food chemistry, Agriculture and Agri-Food Canada, Government of Canada, Kentville, Nova Scotia, Canada.
authors.forename: Wilhelmina
authors.initials: W
authors.lastname: Kalt
authors.affiliation: Department of Nutritional Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Canada.
authors.forename: Chantal
authors.initials: C
authors.lastname: Matar
authors.affiliation: Natural Health Products and Metabolic Diseases Laboratory, Department of Pharmacology and Physiology, Université de Montréal, Station Centre-Ville, P.O. Box 6128, Montréal, Québec, H3C 3J7, Canada. pierre.haddad@umontreal.ca.|Canadian Institutes of Health Research Team in Aboriginal Antidiabetic Medicines and Montreal Diabetes Research Center, Montreal, Canada. pierre.haddad@umontreal.ca.
authors.forename: Pierre S
authors.initials: PS
authors.lastname: Haddad
mesh_terms: D000818:Animals; D029798:Blueberry Plants / Q000737:chemistry*; D002460:Cell Line; D002478:Cells, Cultured; D005285:Fermentation; D005947:Glucose / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats
chemical_list: D010636:Phenols; D010936:Plant Extracts; D005947:Glucose
keywords: Diabetes; Glucose homeostasis; Glucose transport; Glucose-6-phosphatase; Glycogen Synthase