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

近年来，多酚白藜芦醇具有抗癌、抗炎、抗高血糖等多种促进健康的作用。其潜在的机制目前具有很高的科学价值，多种细胞内途径被发现受到白藜芦醇的影响。由于白藜芦醇作为膳食补充剂的潜力，其在肠细胞中的代谢已被广泛地表征为生物利用度，而关于白藜芦醇对营养物质和电解质的肠道吸收的影响的研究却很少。在关于计划项目的初步工作中，我们能够通过在体外用白藜芦醇培养猪肠道组织来证明在功能水平上抑制肠道对葡萄糖的吸收，因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。在白藜芦醇的降糖作用的背景下，这些结果是感兴趣的。计划项目的目的是在功能研究中调查白藜芦醇是否影响肠道对葡萄糖吸收以外的营养物质的吸收。此外，本研究旨在澄清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）的激活已被描述为其促进健康作用的必要条件。与我们初步研究中观察到的肠道葡萄糖吸收的抑制相反，AMPK的激活可能会诱导肠道葡萄糖吸收的增加。关于白藜芦醇的降糖作用，还需要进一步研究白藜芦醇是否激活了所有猪小肠中的AMPK。激活AMPK导致肠道葡萄糖运输抑制的作用可能是基于AMPK介导的膜电位调节，通过影响细胞膜的钾电导作为电致运输过程的驱动力。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。为了研究这一课题，功能研究和表达研究都应该得到应用。白藜芦醇作用独立于细胞内通路的潜在机制是一种直接的转运体-白藜芦醇相互作用。这将分析钠依赖性葡萄糖转运蛋白1。此外，白藜芦醇作为一种亲水性化合物可与细胞膜相互作用。白藜芦醇对转运蛋白活性的影响的可能性是基于白藜芦醇引起的膜微domanes组成的变化。

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.