Resveratrol Inhibits Porcine Intestinal Glucose and Alanine Transport: Potential Roles of Na⁺/K⁺-ATPase Activity, Protein Kinase A, AMP-Activated Protein Kinase and the Association of Selected Nutrient Transport Proteins with Detergent Resistant Membranes

Nutrients. 2018 Mar 3;10(3):302. doi: 10.3390/nu10030302.

Abstract

Background: Beneficial effects of Resveratrol (RSV) have been demonstrated, including effects on transporters and channels. However, little is known about how RSV influences intestinal transport. The aim of this study was to further characterize the effects of RSV on intestinal transport and the respective mechanisms.

Methods: Porcine jejunum and ileum were incubated with RSV (300 µM, 30 min) in Ussing chambers (functional studies) and tissue bathes (detection of protein expression, phosphorylation, association with detergent resistant membranes (DRMs)).

Results: RSV reduced alanine and glucose-induced short circuit currents (ΔIsc) and influenced forskolin-induced ΔIsc. The phosphorylation of sodium-glucose-linked transporter 1 (SGLT1), AMP-activated protein kinase (AMPK), protein kinase A substrates (PKA-S) and liver kinase B1 (LKB1) increased but a causative relation to the inhibitory effects could not directly be established. The DRM association of SGLT1, peptide transporter 1 (PEPT1) and (phosphorylated) Na⁺/H⁺-exchanger 3 (NHE3) did not change.

Conclusion: RSV influences the intestinal transport of glucose, alanine and chloride and is likely to affect other transport processes. As the effects of protein kinase activation vary between the intestinal localizations, it would appear that increasing cyclic adenosine monophosphate (cAMP) levels are part of the mechanism. Nonetheless, the physiological responses depend on cell type-specific structures.

Keywords: AMPK; PKA; SGLT1; Ussing chamber; intestinal transport; phosphorylation.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Alanine / metabolism*
  • Animals
  • Cell Membrane / drug effects*
  • Cell Membrane / enzymology
  • Chlorides / metabolism
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Glucose / metabolism*
  • Ileum / drug effects*
  • Ileum / enzymology
  • In Vitro Techniques
  • Ion Pumps / metabolism*
  • Jejunum / drug effects*
  • Jejunum / enzymology
  • Membrane Potentials
  • Peptide Transporter 1 / metabolism
  • Phosphorylation
  • Resveratrol
  • Sodium-Glucose Transporter 1 / metabolism
  • Sodium-Hydrogen Exchanger 3 / metabolism
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Stilbenes / pharmacology*
  • Sus scrofa

Substances

  • Chlorides
  • Ion Pumps
  • Peptide Transporter 1
  • Sodium-Glucose Transporter 1
  • Sodium-Hydrogen Exchanger 3
  • Stilbenes
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • AMP-Activated Protein Kinases
  • Sodium-Potassium-Exchanging ATPase
  • Glucose
  • Alanine
  • Resveratrol