Abstract : BackgroundGlucose stimulates insulin secretion through a complex metabolic sequence that includes mitochondrial respiration, ATP synthesis and L-type calcium channel (Cav) activation. We and others previously reported that flavonoids regulate glucose-induced insulin secretion by targeting key signaling proteins and cellular processes. Here, we examined the pharmacological behavior of the flavonoid galangin on insulin secretion and we investigated its mechanism by focusing on mitochondrial function.MethodsInsulin secretion experiments were performed in INS-1 β-cell line and rat isolated pancreatic islets. Insulin release was quantified by the homogeneous time-resolved fluorescence (HTRF) method (Cisbio). INS-1 cells oxygen consumption was measured using the high-resolution Oxygraph-2k (OROBOROS Instruments).ResultsGalangin inhibits glucose-induced insulin secretion both in INS-1 cells and in rat isolated pancreatic islets. This flavonoid also inhibits insulin secretion induced by two substrates of mitochondrial metabolism namely leucine and methylsuccinate. In contrast, galangin has no effect on insulin secretion induced by the KATP inhibitor glibenclamide. In line with these findings, we observed that galangin behaves like the mitochondrial oxidative phosphorylation uncoupler CCCP which reduces insulin secretion and increases mitochondrial oxygen consumption rate.ConclusionOur work suggests that galangin inhibits glucose-induced insulin secretion by altering mitochondrial respiration. Therefore, we are currently investigating whether galangin impairs mitochondrial glucose-stimulated ATP synthesis.
https://hal.inrae.fr/hal-02941399 Contributor : Christelle RaynaudConnect in order to contact the contributor Submitted on : Thursday, September 17, 2020 - 9:11:05 AM Last modification on : Friday, June 3, 2022 - 4:20:53 PM Long-term archiving on: : Thursday, December 3, 2020 - 8:59:46 AM
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