title: Procyanidins modify insulinemia by affecting insulin production and degradation.
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.
authors.affiliation: Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Castell-Auví
authors.forename: Lídia
authors.initials: L
authors.lastname: Cedó
authors.forename: Victor
authors.initials: V
authors.lastname: Pallarès
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Blay
authors.forename: Montserrat
authors.initials: M
authors.lastname: Pinent
authors.forename: M José
authors.initials: MJ
authors.lastname: Motilva
authors.forename: Santiago
authors.initials: S
authors.lastname: Garcia-Vallvé
authors.forename: Gerard
authors.initials: G
authors.lastname: Pujadas
authors.forename: Pierre
authors.initials: P
authors.lastname: Maechler
authors.forename: Anna
authors.initials: A
authors.lastname: Ardévol
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D051273:Glucose Transporter Type 2 / Q000235:genetics; D056604:Grape Seed Extract / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000235:genetics; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D007339:Insulysin / Q000235:genetics; D007473:Ion Channels / Q000235:genetics; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics; D044945:Proanthocyanidins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015534:Trans-Activators / Q000235:genetics; D000071246:Uncoupling Protein 2
chemical_list: D051273:Glucose Transporter Type 2; D056604:Grape Seed Extract; D018398:Homeodomain Proteins; D007328:Insulin; D007473:Ion Channels; D024101:Mitochondrial Proteins; D044945:Proanthocyanidins; C495683:Slc2a2 protein, rat; D015534:Trans-Activators; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; C084010:pancreatic and duodenal homeobox 1 protein; D000255:Adenosine Triphosphate; D007339:Insulysin; D005947:Glucose