title: Protocatechuic acid activates key components of insulin signaling pathway mimicking insulin activity.
abstract: METHODS
  Insulin resistance represents an independent risk factor for metabolic and cardiovascular diseases. Researchers have been interested in identifying active harmless compounds, as many insulin-sensitizing drugs have shown unwanted side-effects. It has been demonstrated that anthocyanins and one of their representative metabolites, protocatechuic acid (PCA), ameliorate hyperglycemia, and insulin sensitivity. This study investigated the mechanism of action of PCA responsible for the glucose uptake upregulation.
  
  
  RESULTS
  In human visceral adipocytes, PCA stimulated insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation (+40% with respect to untreated cells) and the downstream events, i.e. phosphoinositide 3-kinase binding to IRS-1 and Akt phosphorylation (+100%, +180%, respectively, with respect to untreated cells). The insulin-like activity of PCA seemed to be mediated by insulin receptor since by inhibiting its autophosphorylation, the PCA effects were completely abolished. Furthermore, PCA was able to activate adenosine monophosphate-activated protein kinase, a serine/threonine kinase whose activation elicits insulin-sensitizing effects.
  
  
  CONCLUSIONS
  This study showed that PCA stimulates the insulin signaling pathway in human adipocytes increasing GLUT4 translocation and glucose uptake. Decreasing insulin resistance is a most desirable aim to be reached for an effective therapeutic/preventive action against metabolic syndrome and type 2 diabetes. Identifying specific food/food components able to improve glucose metabolism can offer an attractive, novel, and economical strategy.
authors.affiliation: Department of Veterinary Public Health and Food Safety, Italian National Institute of Health, Rome, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Scazzocchio
authors.affiliation: Department of Veterinary Public Health and Food Safety, Italian National Institute of Health, Rome, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Varì
authors.affiliation: Department of Veterinary Public Health and Food Safety, Italian National Institute of Health, Rome, Italy.
authors.forename: Carmelina
authors.initials: C
authors.lastname: Filesi
authors.affiliation: Department of Veterinary Public Health and Food Safety, Italian National Institute of Health, Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Del Gaudio
authors.affiliation: Department of Veterinary Public Health and Food Safety, Italian National Institute of Health, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: D'Archivio
authors.affiliation: Department of Veterinary Public Health and Food Safety, Italian National Institute of Health, Rome, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Santangelo
authors.affiliation: "Fabia Mater" Hospital, Rome, Italy.
authors.forename: Annunziata
authors.initials: A
authors.lastname: Iacovelli
authors.affiliation: Department of Biological Chemistry, Medical Chemistry and Molecular Biology, University of Catania, Catania, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Galvano
authors.affiliation: IRCCS "S. Donato" Hospital, San Donato Milanese, Milan, Italy.
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Pluchinotta
authors.affiliation: Department of Veterinary Public Health and Food Safety, Italian National Institute of Health, Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Giovannini
authors.affiliation: Department of Veterinary Public Health and Food Safety, Italian National Institute of Health, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Masella
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D065567:Absorption, Physiological / Q000187:drug effects; D002478:Cells, Cultured; D019587:Dietary Supplements; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000819:agonists / Q000378:metabolism; D006801:Humans; D062385:Hydroxybenzoates / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000009:adverse effects; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D051275:Glucose Transporter Type 4; D062385:Hydroxybenzoates; D007004:Hypoglycemic Agents; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D008077:Lipoproteins, LDL; D000081082:Phosphoinositide-3 Kinase Inhibitors; C495692:SLC2A4 protein, human; C099252:oxidized low density lipoprotein; C009091:protocatechuic acid; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: Adipocytes; Diet; Functional food; Insulin resistance; Insulin signaling