title: Grape seed procyanidins improve β-cell functionality under lipotoxic conditions due to their lipid-lowering effect.
abstract: 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.
authors.affiliation: Nutrigenomics Research Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Marcel·lí Domingo s/n, 43007 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: Mayte
authors.initials: M
authors.lastname: Blay
authors.forename: Montserrat
authors.initials: M
authors.lastname: Pinent
authors.forename: Anna
authors.initials: A
authors.lastname: Ardévol
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D002096:C-Peptide / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D003470:Culture Media; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D056604:Grape Seed Extract / Q000494:pharmacology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D050356:Lipid Metabolism; D044945:Proanthocyanidins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002096:C-Peptide; D003470:Culture Media; D005227:Fatty Acids; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D018398:Homeodomain Proteins; D007328:Insulin; D044945:Proanthocyanidins; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D002334:Carnitine O-Palmitoyltransferase; D054890:Fatty Acid Synthase, Type I; D005947:Glucose