Urolithin C increases glucose-induced ERK activation which contributes to insulin secretion
| Autor: | Jérémie Neasta, Gérard Cros, Slimane Toubal, Morgane Bayle, Catherine Oiry |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Pharmacology
MAPK/ERK pathway Mitogen-Activated Protein Kinase 3 Kinase Activator (genetics) Metabolite 030226 pharmacology & pharmacy Hydrolyzable Tannins Urolithin Cell biology Cell Line Rats 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Glucose chemistry Insulin-Secreting Cells Insulin Secretion Extracellular Phosphorylation Animals Pharmacology (medical) 030217 neurology & neurosurgery Ellagic acid |
| Zdroj: | Fundamentalclinical pharmacologyREFERENCES. 34(5) |
| ISSN: | 1472-8206 |
| Popis: | 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 Ca2+ channel opening and Ca2+ 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. |
| Databáze: | OpenAIRE |
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