Resveratrol Influences Pancreatic Islets by Opposing Effects on Electrical Activity and Insulin Release
| Autor: | Theresa Hoffmeister, Lisa Schönhoff, Martina Düfer, Simone Brouwer, Anne Gresch |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
endocrine system diseases medicine.medical_treatment Resveratrol Pharmacology Membrane Potentials Islets of Langerhans Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Sirtuin 1 Insulin Secretion Cyclic AMP medicine Animals Guanine Nucleotide Exchange Factors geography geography.geographical_feature_category biology Pancreatic islets Insulin food and beverages Long-term potentiation Depolarization Islet Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure chemistry biology.protein Calcium hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Intracellular Food Science Biotechnology |
| Zdroj: | Molecular Nutrition & Food Research. 62:1700902 |
| ISSN: | 1613-4125 |
| DOI: | 10.1002/mnfr.201700902 |
| Popis: | 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 Ca2+ concentration by fluorescence methods. Resveratrol (25 μmol L-1 ) elevates [Ca2+ ]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 KATP 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. |
| Databáze: | OpenAIRE |
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