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Scientific article
English

Procyanidins modify insulinemia by affecting insulin production and degradation

Published inThe Journal of nutritional biochemistry, vol. 23, no. 12, p. 1565-1572
Publication date2012
Abstract

Previous studies from our research group have suggested that procyanidins modify glycemia and insulinemia. The aim of this work was to evaluate the effects of procyanidins on β-cell functionality in a nonpathological system. Four groups of healthy rats were studied. The animals were given daily acute doses of grape seed procyanidin extract (GSPE) for different time periods and at different daily amounts. A β-cell line (INS-1E) was treated with 25 mg GSPE/L for 24 h to identify possible mechanisms of action for the procyanidins. In vivo experiments showed that different doses of GSPE affected insulinemia in different ways by modifying β-cell functionality and/or insulin degradation. The islets isolated from rats that were treated with 25 mg GSPE/kg of body weight for 45 days exhibited a limited response to glucose stimulation. In addition, insulin gene expression, insulin synthesis and expression of genes related to insulin secretion were all down-regulated. In vitro studies revealed that GSPE decreased the ability of β-cells to secrete insulin in response to glucose. GSPE increased glucose uptake in β-cells under high-glucose conditions but impaired glucose-induced mitochondrial hyperpolarization, decreased adenosine triphosphate (ATP) synthesis and altered cellular membrane potentials. GSPE also modified Glut2, glucokinase and Ucp2 gene expression as well as altered the expression of hepatic insulin-degrading enzyme (Ide), thereby altering insulin degradation. At some doses, procyanidins changed β-cell functionality by modifying insulin synthesis, secretion and degradation under nonpathological conditions. Membrane potentials and Ide provide putative targets for procyanidins to induce these effects.

Keywords
  • Adenosine Triphosphate/metabolism
  • Animals
  • Cell Line
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation/drug effects
  • Glucose/metabolism/pharmacology
  • Glucose Transporter Type 2/genetics
  • Grape Seed Extract/pharmacology
  • Homeodomain Proteins/genetics
  • Insulin/genetics/metabolism/secretion
  • Insulin-Secreting Cells/drug effects/metabolism
  • Insulysin/genetics
  • Ion Channels/genetics
  • Islets of Langerhans/drug effects/metabolism
  • Membrane Potentials/drug effects
  • Mitochondria/drug effects/metabolism
  • Mitochondrial Proteins/genetics
  • Proanthocyanidins/pharmacology
  • Rats
  • Rats, Wistar
  • Trans-Activators/genetics
Citation (ISO format)
CASTELL-AUVÍ, Anna et al. Procyanidins modify insulinemia by affecting insulin production and degradation. In: The Journal of nutritional biochemistry, 2012, vol. 23, n° 12, p. 1565–1572. doi: 10.1016/j.jnutbio.2011.10.010
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Article (Published version)
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Identifiers
ISSN of the journal0955-2863
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