Blackcurrant Extract Ameliorates Hyperglycemia in Type 2 Diabetic Mice in Association with Increased Basal Secretion of Glucagon-Like Peptide-1 and Activation of AMP-Activated Protein Kinase

J Nutr Sci Vitaminol (Tokyo). 2018;64(4):258-264. doi: 10.3177/jnsv.64.258.

Abstract

Blackcurrants are berries that contain high levels of anthocyanins, particularly delphinidin 3-rutinoside (D3R). Several studies have reported that the consumption of blackcurrant extract (BCE) lowers blood glucose levels and ameliorates glucose tolerance, but the mechanism underlying this effect remains unclear. Glucagon-like peptide-1 (GLP-1) and AMP-activated protein kinase (AMPK) are considered one of the most significant molecular targets for the prevention and treatment of type 2 diabetes. In this study, we showed that dietary BCE significantly reduced blood glucose concentration and improved glucose tolerance in type 2 diabetic mice (KK-Ay). The basal GLP-1 concentration in plasma was significantly increased in the BCE group accompanied by upregulation of prohormone convertase 1/3 (PC1/3), the enzyme that processes intestinal proglucagon. Moreover, the level of phospho-AMPKα protein in skeletal muscle was significantly increased in the BCE group, and this was increase accompanied by significant upregulation of glucose transporter 4 (Glut4) proteins in the plasma membrane of BCE group. In conclusion, dietary BCE significantly reduced blood glucose concentration and improved glucose tolerance in association with increased basal GLP-1 concentration in plasma, upregulation of PC1/3 expression, and translocation of Glut4 to the plasma membrane of skeletal muscle in type 2 diabetic mice; furthermore, these effects were accompanied by activation of AMPK. Our findings demonstrated that D3R-rich BCE may help prevent diabetes and allow the dosages of diabetes drugs to be reduced.

Keywords: AMP-activated protein kinase; blackcurrant extract; delphinidin 3-rutinoside; diabetes; glucagon-like peptide-1.

MeSH terms

  • AMP-Activated Protein Kinases / chemistry
  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Cell Membrane / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / therapy*
  • Dietary Supplements* / analysis
  • Enzyme Activation
  • Enzyme Induction
  • Fruit / chemistry
  • Glucagon-Like Peptide 1 / agonists*
  • Glucagon-Like Peptide 1 / metabolism
  • Glucose Transporter Type 4 / agonists
  • Glucose Transporter Type 4 / metabolism
  • Hypoglycemic Agents / analysis
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / therapeutic use*
  • Ileum / enzymology
  • Ileum / metabolism
  • Intestinal Mucosa / enzymology
  • Intestinal Mucosa / metabolism
  • Isoenzymes / chemistry
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Male
  • Mice, Mutant Strains
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / therapeutic use*
  • Proprotein Convertases / chemistry
  • Proprotein Convertases / genetics
  • Proprotein Convertases / metabolism
  • Protein Transport
  • Ribes / chemistry*
  • Specific Pathogen-Free Organisms

Substances

  • Glucose Transporter Type 4
  • Hypoglycemic Agents
  • Isoenzymes
  • Plant Extracts
  • Slc2a4 protein, mouse
  • Glucagon-Like Peptide 1
  • AMP-Activated Protein Kinases
  • Proprotein Convertases