Publications (29) View all
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Article: Grape seed procyanidin extract modulates proliferation and apoptosis of pancreatic beta-cells.
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ABSTRACT: Grape seed procyanidin extract (GSPE) modulates glucose homeostasis and insulinemia in several animal models. Under pathological conditions, insulin levels are dependent on pancreatic beta-cell functionality, as well as on the beta-cell mass expansion or apoptosis in the pancreas. In this study, we analysed the effects of GSPE on modulating apoptosis and proliferation in beta-cells. We tested the effects of GSPE in the INS-1E pancreatic beta-cell line, either under basal or altered conditions with high glucose, insulin or palmitate levels. GSPE enhanced the pro-apoptotic effect of high glucose and showed clear antiproliferative effects under high glucose, insulin and palmitate conditions. These antiproliferative effects are likely due to high molecular weight compounds contained in the extract. GSPE also modulated pro- and anti-apoptotic markers in the pancreas of rats fed a cafeteria diet, with the effect depending on the dose of GSPE and duration of treatment. Thus, GSPE is able to modulate apoptosis and proliferation of beta-cells under altered, but not basal, conditions.Food Chemistry 05/2013; 138(1):524-30. · 3.65 Impact Factor -
Article: Grape seed procyanidin extract reduces the endotoxic effects induced by lipopolysaccharides in rats.
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ABSTRACT: Acute inflammation is a response to injury, infection, tissue damage or shock. Bacterial lipopolysaccharide (LPS) is an endotoxin implicated in triggering sepsis and septic shock, and LPS promotes the inflammatory response resulting in the secretion of proinflammatory and anti-inflammatory cytokines such as the interleukins (IL-6, IL-1β and IL-10) and tumor necrosis factor-alpha (TNF-α) by the immune cells. Furthermore, nitric oxide (NO) and reactive oxygen species (ROS) levels increase rapidly, which is partially due to the activation of inducible nitric oxide synthase (iNOS) in several tissues in response to inflammatory stimuli. Previous studies have shown that procyanidins, polyphenols present in foods such as apples, grapes, cocoa and berries, have several beneficial properties against inflammation and oxidative stress using several in vitro and in vivo models. In the current study, the anti-inflammatory and antioxidant effects of two physiological doses and two pharmaceutical doses of grape seed procyanidin extract (GSPE) were analyzed using a rat model of septic shock by the intraperitoneal injection of LPS derived from E. coli. The high nutritional (75mg/kg⁎day) and the high pharmacological doses (200mg/kg⁎day) of GSPE showed anti-inflammatory effects by decreasing the proinflammatory marker NOx in the plasma, red blood cells, spleen and liver. Moreover, the high pharmacological dose also down-regulated the genes Il-6 and iNos; and the high nutritional dose increased the glutathione ratio (SGGS/Total glutathione) further illustrating the antioxidant capability of GSPE. In conclusion, several doses of GSPE can alleviate acute inflammation triggered by LPS in rats at the systemic and local levels when administered for as few as 15 days prior the injection of endotoxin.Free radical biology & medicine 02/2013; · 5.42 Impact Factor -
Article: Procyanidins Modulate MicroRNA Expression in Pancreatic Islets.
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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; · 2.82 Impact Factor -
Article: Pancreatic islet proteome profile in Zucker fatty rats chronically treated with a grape seed procyanidin extract.
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ABSTRACT: Grape seed procyanidin extract (GSPE) has been reported to modify glucose metabolism and β-cell functionality through its lipid-lowering effects in a diet-induced obesity model. The objective of the present study was to evaluate the effects of chronically administrated GSPE on the proteomic profile of pancreatic islets from Zucker fatty (ZF) rats. An isobaric tag for relative and absolute quantitation (iTRAQ) experiment was conducted and 31 proteins were found to be differentially expressed in ZF rats treated with GSPE compared to untreated ZF rats. Of these proteins, five subcategories of biological processes emerged: hexose metabolic processes, response to hormone stimulus, apoptosis and cell death, translation and protein folding, and macromolecular complex assembly. Gene expression analysis supported the role of the first three biological processes, concluding that GSPE limits insulin synthesis and secretion and modulates factors involved in apoptosis, but these molecular changes are not sufficient to counteract the genetic background of the Zucker model at a physiological level.Food Chemistry 12/2012; 135(3):1948-56. · 3.65 Impact Factor -
Article: Grape seed procyanidins improve β-cell functionality under lipotoxic conditions due to their lipid-lowering effect.
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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; · 4.29 Impact Factor
