Activating Effects of Phenolics from Apache Red Zea mays L. on Free Fatty Acid Receptor 1 and Glucokinase Evaluated with a Dual Culture System with Epithelial, Pancreatic, and Liver Cells

J Agric Food Chem. 2019 Aug 21;67(33):9148-9159. doi: 10.1021/acs.jafc.8b06642. Epub 2019 Mar 5.

Abstract

The aim was to characterize a phenolic-rich water extract from the pericarp of an improved genotype of Apache red maize (RPE) and evaluate its ability to activate the type 2 diabetes markers free fatty acid receptor 1 (GPR40) and glucokinase (GK) in vitro. The extract contained mainly phenolic acids, anthocyanins, and other flavonoids. RPE inhibited α-amylase (IC50 = 88.3 μg/mL), α-glucosidase (IC50 = 169.3 μg/mL), and reduced glucose transport in a Caco-2 cell monolayer (up to 25%). Furthermore, RPE activated GPR40 (EC50 = 77.7 μg/mL) in pancreatic INS-1E cells and GK (EC50 = 43.4 μg/mL) in liver HepG2 cells, potentially through allosteric modulation. RPE activated GPR40-related insulin secretory pathway and activated the glucose metabolism regulator AMPK (up to 78%). Our results support the hypothesis that foods with a high concentration of anthocyanins and phenolic acids, such as in the selected variety of maize used, could ameliorate obesity and type 2 diabetes comorbidities.

Keywords: anthocyanins; colored maize; free fatty acid receptor 1; type 2 diabetes.

MeSH terms

  • Anthocyanins / chemistry
  • Anthocyanins / isolation & purification
  • Anthocyanins / pharmacology*
  • Biological Transport / drug effects
  • Caco-2 Cells
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Flavonoids / chemistry
  • Flavonoids / isolation & purification
  • Flavonoids / pharmacology*
  • Glucokinase / antagonists & inhibitors*
  • Glucokinase / metabolism
  • Glucose / metabolism
  • Hep G2 Cells
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Humans
  • Hydroxybenzoates / chemistry
  • Hydroxybenzoates / isolation & purification
  • Hydroxybenzoates / pharmacology*
  • Insulin / metabolism
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Liver / cytology
  • Liver / drug effects
  • Liver / metabolism
  • Molecular Docking Simulation
  • Pancreas / cytology
  • Pancreas / drug effects
  • Pancreas / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Zea mays / chemistry*
  • Zea mays / genetics
  • alpha-Amylases / antagonists & inhibitors
  • alpha-Amylases / metabolism

Substances

  • Anthocyanins
  • FFAR1 protein, human
  • Flavonoids
  • Hydroxybenzoates
  • Insulin
  • Plant Extracts
  • Receptors, G-Protein-Coupled
  • Glucokinase
  • alpha-Amylases
  • phenolic acid
  • Glucose