Studies on effects and mechanisms of trans-resveratrol on intestinal nutrient transport in the porcine small intestines

反式白藜芦醇对猪小肠肠道营养转运的影响及机制研究

• 批准号: 274408141
• 负责人: Dr. Stefanie Klinger
• 金额: --
• 依托单位: Institut für Physiologie und Zellbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/274408141?language=en
• 关键词: Studies; effects; mechanisms; trans; resveratrol

In recent years, several health promoting effects have been described for the polyphenol resveratrol including anti-carcinogenic, anti-inflammatory and anti-hyperglycemic properties. The underlying mechanisms are of high scientific interest at the moment and a variety of intracellular pathways was found to be influenced by resveratrol. Because of the potential of resveratrol to be used as a dietary supplement, its metabolism in enterocytes has been intensively characterized with regard to its bioavailability, whereas only few studies are available on effects of resveratrol on the intestinal absorption of nutrients and electrolytes. In preliminary work with regard to the planned project, we were able to demonstrate an inhibition of the intestinal absorption of glucose on the functional level by incubating porcine intestinal tissues with resveratrol in vitro, whereby this effect seems to be, at least partly, attributable to mechanisms independent from influencing intracellular pathways. In the context of an antihyperglycemic action of resveratrol, these results are of interest. The aim of the planned project is to investigate in functional studies, whether the intestinal absorption of nutrients apart from the absorption of glucose is influenced by resveratrol. Additionally, the study aims at clarifying some aspects of the underlying mechanisms. In the current literature, a resveratrol-mediated activation of AMP activated protein kinase (AMPK) has been described to be essential for its health promoting effects. In contrast to the inhibition of the intestinal glucose absorption observed in our preliminary studies, the activation of AMPK is likely to induce an increase in the intestinal glucose absorption. With regard to the antihyperglycemic properties of resveratrol it should be investigated whether AMPK is activated by resveratrol at all porcine small intestines. An effect of activated AMPK leading to an inhibition of intestinal glucose transport may be based on an AMPK-mediated modulation of the membrane potential as the driving force for electrogenic transport processes via influencing the potassium conductance of the cell membrane. However, such a modulation of the membrane potential may also be based on direct effects of resveratrol on potassium channels. Both, functional and expression studies should be applied in order to investigate this topic. A potential mechanism that may contribute to the effects of resveratrol independent from intracellular pathways is a direct transporter-resveratrol-interaction. This will be analysed for the sodium dependent glucose transporter 1. Additionally, resveratrol as a hydrophilic compound may interact with the cell membrane. The possibility that effects of resveratrol on the activity of transport proteins are based on resveratrol induced changes in the composition of membrane microdomanes will be analysed.

近年来，已经描述了多酚白藜芦醇的几种健康促进作用，包括抗癌、抗炎和抗高血糖特性。其潜在机制目前具有很高的科学兴趣，并且发现多种细胞内途径受到白藜芦醇的影响。由于白藜芦醇可用作膳食补充剂的潜力，其在肠细胞中的代谢已被集中表征其生物利用度，而关于白藜芦醇对肠道吸收营养素和电解质的影响的研究很少。在计划项目的初步工作中，我们能够证明通过在体外用白藜芦醇孵育猪肠组织在功能水平上抑制葡萄糖的肠吸收，由此这种效果似乎至少部分归因于独立于影响细胞内途径的机制。在白藜芦醇的抗高血糖作用的背景下，这些结果是有趣的。计划项目的目的是在功能研究中调查，除了葡萄糖的吸收外，肠道对营养物质的吸收是否受到白藜芦醇的影响。此外，该研究旨在阐明潜在机制的某些方面。在目前的文献中，白藜芦醇介导的AMP活化蛋白激酶（AMPK）的活化已被描述为其健康促进作用所必需。与我们的初步研究中观察到的肠道葡萄糖吸收的抑制相反，AMPK的激活可能诱导肠道葡萄糖吸收的增加。关于白藜芦醇的抗高血糖特性，应研究白藜芦醇是否在所有猪小肠中激活AMPK。激活的AMPK导致肠葡萄糖转运抑制的作用可能是基于AMPK介导的膜电位调节，其通过影响细胞膜的钾电导作为生电转运过程的驱动力。然而，这种膜电位的调节也可能是基于白藜芦醇对钾通道的直接作用。为了研究这一主题，应该应用功能和表达研究。白藜芦醇作用的一个潜在机制是直接的转运蛋白-白藜芦醇相互作用。将对钠依赖性葡萄糖转运蛋白1进行分析。此外，白藜芦醇作为亲水性化合物可与细胞膜相互作用。将分析白藜芦醇对转运蛋白活性的影响是基于白藜芦醇诱导膜微区组成的变化的可能性。