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

• Applicant: Dr. Stefanie Klinger
• Subject Area: Veterinary Medical Science
• Term: from 2015 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 274408141

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.

• DFG Programme: Research Grants