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Resveratrol Influences Pancreatic Islets by Opposing Effects on Electrical Activity and Insulin Release
Author(s) -
Brouwer Simone,
Hoffmeister Theresa,
Gresch Anne,
Schönhoff Lisa,
Düfer Martina
Publication year - 2018
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201700902
Subject(s) - resveratrol , medicine , insulin , endocrinology , chemistry , depolarization , intracellular , islet , pancreatic islets , glipizide , biology , biochemistry
Scope Resveratrol is suggested to improve glycemic control by activation of sirtuin 1 (SIRT1) and has already been tested clinically. Our investigation characterizes the targets of resveratrol in pancreatic beta cells and their contribution to short‐ and long‐term effects on insulin secretion. Methods and results Islets or beta cells are isolated from C57BL/6N mice. Electrophysiology is performed with microelectrode arrays and patch‐clamp technique, insulin secretion and content are determined by radioimmunoassay, cAMP is measured by enzyme‐linked immunosorbent assay, and cytosolic Ca 2+ concentration by fluorescence methods. Resveratrol (25 μmol L –1 ) elevates [Ca 2+ ] c and potentiates glucose‐stimulated insulin secretion. These effects are associated with increased intracellular cAMP and are sensitive to the SIRT1 blocker Ex‐527. Inhibition of EPAC1 by CE3F4 also abolishes the stimulatory effect of resveratrol. The underlying mechanism does not involve membrane depolarization as resveratrol even reduces electrical activity despite blocking K ATP channels. Importantly, after prolonged exposure to resveratrol (14 days), the beneficial influence of the polyphenol on insulin release is lost. Conclusion Resveratrol addresses multiple targets in pancreatic islets. Potentiation of insulin secretion is mediated by SIRT1‐dependent activation of cAMP/EPAC1. Considering resveratrol as therapeutic supplement for patients with type 2 diabetes mellitus, the inhibitory influence on electrical excitability attenuates positive effects.