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.
- SourceAvailable from: Núria Taltavull
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- "There is wide interest in the development of strategies for the prevention of MetS, mainly via two different approaches: a) pharmacology – based on the use of drugs such as certain statins or AMPK (5′ adenosine monophosphate-activated protein kinase) activating agents , ; and b) nutrition–based on diet supplementation with functional compounds, e.g., proanthocyanidins  or iminosugars . "
ABSTRACT: SHROB rats have been suggested as a model for metabolic syndrome (MetS) as a situation prior to the onset of CVD or type-2 diabetes, but information on descriptive biochemical parameters for this model is limited. Here, we extensively evaluate parameters related to CVD and oxidative stress (OS) in SHROB rats. SHROB rats were monitored for 15 weeks and compared to a control group of Wistar rats. Body weight was recorded weekly. At the end of the study, parameters related to CVD and OS were evaluated in plasma, urine and different organs. SHROB rats presented statistically significant differences from Wistar rats in CVD risk factors: total cholesterol, LDL-cholesterol, triglycerides, apoA1, apoB100, abdominal fat, insulin, blood pressure, C-reactive protein, ICAM-1 and PAI-1. In adipose tissue, liver and brain, the endogenous antioxidant systems were activated, yet there was no significant oxidative damage to lipids (MDA) or proteins (carbonylation). We conclude that SHROB rats present significant alterations in parameters related to inflammation, endothelial dysfunction, thrombotic activity, insulin resistance and OS measured in plasma as well as enhanced redox defence systems in vital organs that will be useful as markers of MetS and CVD for nutrition interventions.PLoS ONE 08/2014; 9(8):e104637. DOI:10.1371/journal.pone.0104637 · 3.23 Impact Factor
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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.The Journal of nutritional biochemistry 09/2012; 24(6). DOI:10.1016/j.jnutbio.2012.06.015 · 3.79 Impact Factor
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ABSTRACT: Procyanidins modulate glucose metabolism, partly due, to its effects on pancreas. Given the role of microRNAs (miRNAs) in the regulation of diabetes and the fact that flavonoids modulate miRNAs in other tissues, we hypothesized that procyanidins might target miRNAs in the pancreas. We investigated the miRNA expression profile in pancreatic islets isolated from rats treated with a daily dose of grape seed procyanidin extract (GSPE) (25 mg/kg of body weight) for 45 days. The miRWalk database identified putative target genes of these miRNAs. We found that GSPE altered significantly the expression of miR-1249, miR-483, miR-30c-1*, and miR-3544. In silico prediction studies suggested that ion transport and response to glucose are among the regulated pathways. As a conclusion, this is the first study showing that procyanidins can also exert their bioactivity on pancreatic islets by modifying the miRNA expression pattern.Journal of Agricultural and Food Chemistry 12/2012; 61(2). DOI:10.1021/jf303972f · 2.91 Impact Factor