Résumé
Abstract Polyphenols exert pharmacological actions through protein‐mediated mechanisms and by modulating intracellular signalling pathways. We recently showed that a gut‐microbial metabolite of ellagic acid named urolithin C is a glucose‐dependent activator of insulin secretion acting by facilitating L‐type Ca 2+ channel opening and Ca 2+ influx into pancreatic β‐cells. However, it is still unknown whether urolithin C regulates key intracellular signalling proteins in β‐cells. Here, we report that urolithin C enhanced glucose‐induced extracellular signal‐regulated kinases 1/2 (ERK1/2) activation as shown by higher phosphorylation levels in INS‐1 β‐cells. Interestingly, inhibition of ERK1/2 with two structurally distinct inhibitors led to a reduction in urolithin C effect on insulin secretion. Finally, we provide data to suggest that urolithin C‐mediated ERK1/2 phosphorylation involved insulin signalling in INS‐1 cells. Together, these data indicate that the pharmacological action of urolithin C on insulin secretion relies, in part, on its capacity to enhance glucose‐induced ERK1/2 activation. Therefore, our study extends our understanding of the pharmacological action of urolithin C in β‐cells. More generally, our findings revealed that urolithin C modulated the activation of key multifunctional intracellular signalling kinases which participate in the regulation of numerous biological processes.