Grape seed procyanidins improve β-cell functionality under lipotoxic conditions due to their lipid-lowering effect

J Nutr Biochem. 2013 Jun;24(6):948-53. doi: 10.1016/j.jnutbio.2012.06.015. Epub 2012 Sep 17.


Procyanidins have positive effects on glucose metabolism in conditions involving slightly disrupted glucose homeostasis, but it is not clear how procyanidins interact with β-cells. In this work, we evaluate the effects of procyanidins on β-cell functionality under an insulin-resistance condition. After 13 weeks of cafeteria diet, female Wistar rats were treated with 25 mg of grape seed procyanidin extract (GSPE)/kg of body weight (BW) for 30 days. To determine the possible mechanisms of action of procyanidins, INS-1E cells were separately incubated in high-glucose, high-insulin and high-oleate media to reproduce the conditions the β-cells were subjected to during the cafeteria diet feeding. In vivo experiments showed that chronic GSPE treatment decreased insulin production, since C-peptide levels and insulin protein levels in plasma were lower than those of cafeteria-fed rats, as were insulin and Pdx1 mRNA levels in the pancreas. GSPE effects observed in vivo were reproduced in INS-1E cells cultured with high oleate for 3 days. GSPE treatment significantly reduces triglyceride content in β-cells treated with high oleate and in the pancreas of cafeteria-fed rats. Moreover, gene expression analysis of the pancreas of cafeteria-fed rats revealed that procyanidins up-regulated the expression of Cpt1a and down-regulated the expression of lipid synthesis-related genes such as Fasn and Srebf1. Procyanidin treatment counteracted the decrease of AMPK protein levels after cafeteria treatment. Procyanidins cause a lack of triglyceride accumulation in β-cells. This counteracts its negative effects on insulin production, allowing for healthy levels of insulin production under hyperlipidemic conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology*
  • C-Peptide / metabolism
  • Carnitine O-Palmitoyltransferase / genetics
  • Carnitine O-Palmitoyltransferase / metabolism
  • Culture Media
  • Fatty Acid Synthase, Type I / genetics
  • Fatty Acid Synthase, Type I / metabolism
  • Fatty Acids / metabolism
  • Female
  • Glucose / metabolism
  • Grape Seed Extract / pharmacology*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Insulin / metabolism
  • Insulin Resistance
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Lipid Metabolism
  • Proanthocyanidins / pharmacology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism


  • Antioxidants
  • C-Peptide
  • Culture Media
  • Fatty Acids
  • Grape Seed Extract
  • Grape Seed Proanthocyanidins
  • Homeodomain Proteins
  • Insulin
  • Proanthocyanidins
  • RNA, Messenger
  • Sterol Regulatory Element Binding Protein 1
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein
  • Carnitine O-Palmitoyltransferase
  • Fatty Acid Synthase, Type I
  • Glucose