Protocatechuic acid activates key components of insulin signaling pathway mimicking insulin activity

Mol Nutr Food Res. 2015 Aug;59(8):1472-81. doi: 10.1002/mnfr.201400816. Epub 2015 May 29.

Abstract

Scope: 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.

Methods and 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.

Conclusion: 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.

Keywords: Adipocytes; Diet; Functional food; Insulin resistance; Insulin signaling.

MeSH terms

  • AMP-Activated Protein Kinases / antagonists & inhibitors
  • AMP-Activated Protein Kinases / chemistry
  • AMP-Activated Protein Kinases / metabolism
  • Absorption, Physiological / drug effects
  • Cells, Cultured
  • Dietary Supplements
  • Enzyme Inhibitors / pharmacology
  • Glucose / metabolism
  • Glucose Transporter Type 4 / agonists
  • Glucose Transporter Type 4 / metabolism
  • Humans
  • Hydroxybenzoates / antagonists & inhibitors
  • Hydroxybenzoates / metabolism*
  • Hypoglycemic Agents / antagonists & inhibitors
  • Hypoglycemic Agents / metabolism*
  • Insulin Receptor Substrate Proteins / agonists*
  • Insulin Receptor Substrate Proteins / antagonists & inhibitors
  • Insulin Receptor Substrate Proteins / metabolism
  • Insulin Resistance*
  • Intra-Abdominal Fat / cytology
  • Intra-Abdominal Fat / drug effects
  • Intra-Abdominal Fat / metabolism*
  • Lipoproteins, LDL / adverse effects
  • Phosphatidylinositol 3-Kinase / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation
  • Protein Processing, Post-Translational* / drug effects
  • Protein Transport / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction* / drug effects

Substances

  • Enzyme Inhibitors
  • Glucose Transporter Type 4
  • Hydroxybenzoates
  • Hypoglycemic Agents
  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • Lipoproteins, LDL
  • Phosphoinositide-3 Kinase Inhibitors
  • SLC2A4 protein, human
  • oxidized low density lipoprotein
  • protocatechuic acid
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • AMP-Activated Protein Kinases
  • Glucose