Résumé
Pancreatic β-cell function and notably glucose-induced insulin secretion play a pivotal role in glucose homeostasis. We have previously shown that natural molecules like flavonoids or ellagitannin metabolites potentiate glucose-induced insulin secretion through a mechanism implicating the activation of L-type Ca2 + (CaV) channels and ERK1/2 kinase. In this study, we isolated a coumarin imperatorin from the roots of Angelica archangelica L. and investigated its effect on insulin secretion modulation. Material and methods: Imperatorin was isolated from the roots of A. archangelica L., through Soxhlet extraction in n-hexane, and column and preparative chromatography methods. The structure of the compound was analyzed and confirmed using High-Pressure Liquid Chromatography Diode Array Detector Electrospray Ionization Tandem Mass Spectrometry and Nuclear Magnetic Resonance methods. Pharmacological experiments were performed INS-1 β-cell line. Insulin release was quantified by the homogeneous time-resolved fluorescence (HTRF) method. Mechanism of action will be studied using western blot and/or patch clamp techniques. Results: The effects of imperatorin have been tested on insulin secretion in INS-1 cells. Increasing concentrations were tested under basal (1.4mM) or stimulating (8.3mM) glucose conditions. Under basal condition, we observed a modest increase in insulin secretion at the highest concentration. As expected, 8.3mM glucose induced a significant insulin secretion. Imperatorin potentiated 8.3mM glucose-induced insulin secretion in a concentration-dependent manner. Regarding the mechanism of action, in relation of previous results, the effects of imperatorin on ERK1/2 activation and CaV currents are under investigation in INS-1 cells. Discussion/Conclusion: Imperatorin may modulate insulin secretion in pancreatic β-cells in a glucose dependent manner.