Original Paper

Resveratrol Inhibits Electrical Activity and Insulin Release from Insulinoma Cells by Block of Voltage-Gated Ca²⁺ Channels and Swelling-Dependent Cl^- Currents
Martin Jakab¹, Sibylle Lach¹, Zuzana Bacová², Christian Langelüddecke¹, Vladimir Strbák², Sabine Schmidt¹, Eva Iglseder¹, Markus Paulmichl³, John Geibel⁴, Markus Ritter<sup>1

1</sup>Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg,
²Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava,
³Institute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg,
⁴Department of Surgery and Department of Cellular and Molecular Physiology, Yale University, School of Medicine, New Haven, CT

Address of Corresponding Author

Cell Physiol Biochem 2008;22:567-578 (DOI: 10.1159/000185541)

  Key Words

• Insulin
• Resveratrol
• Voltage-dependent calcium channel
• Swelling-dependent chloride current
• INS-1E

  Abstract

The phytostilbene resveratrol (RV) improves the metabolic state in animal models by increasing the insulin responsiveness of tissues and there is evidence that RV affects insulin secretion from native -cells and insulinoma cells. In whole cell patch clamp experiments on clonal rat INS-1E cells we used high extracellular glucose (20 mM), extracellular hypotonicity (30%) or tolbutamide (100 µM) to elicit membrane depolarizations and electrical activity. Application of RV (50 µM) repolarized the cells, terminated electrical activity and prevented the hypotonicity-induced depolarization. These effects were fully reversible and intermittent application of RV restored tolbutamide-induced electrical activity after desensitization. Glucose-induced depolarization was counteracted by RV in presence of iberiotoxin (50 nM), showing that the RV effect does not depend on BK_Ca channel activation. RV dose-dependently inhibited K_ATP currents, L- and T-type Ca²⁺ currents and swelling-dependent Cl^- currents evoked by either hypotonicity or high extracellular glucose - ion conductances crucially involved in regulating the electrical activity of insulin secreting cells. We further show that RV blunts glucose-induced, but not basal insulin release. Our results indicate that RV counteracts/prevents stimulus-induced cell membrane depolarization and electrical activity by blocking voltage-gated Ca²⁺- and swelling-dependent Cl^- currents despite the inhibition of K_ATP currents.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

Markus Ritter, MD
Institute of Physiology and Pathophysiology, Paracelsus Medical University
Strubergasse 21, 5020 Salzburg (Austria)
Tel. +43 662 442002 1251, Fax: +43 662 442002 1259
E-Mail markus.ritter@pmu.ac.at

  Article Information

Accepted: July 21, 2008
Published online: December 09, 2008
Number of Print Pages : 12