Myricetin Amplifies Glucose–Stimulated Insulin Secretion via the cAMP-PKA-Epac-2 Signaling Cascade
<b>Aim</b>: Myricetin, a natural bioflavonoid, is reported as an anti-diabetic agent since it possesses the ability to inhibit α-glucosidase activity, stimulate insulin action and secretion, manage ROS, and prevent diabetes complications. Myricetin was identified as a new insulin secreta...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
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| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/13/6/1447 |
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| Summary: | <b>Aim</b>: Myricetin, a natural bioflavonoid, is reported as an anti-diabetic agent since it possesses the ability to inhibit α-glucosidase activity, stimulate insulin action and secretion, manage ROS, and prevent diabetes complications. Myricetin was identified as a new insulin secretagogue that enhances glucose-stimulated insulin secretion and seems like a better antidiabetic drug candidate. Here, we explored the insulinotropic mechanism(s) of myricetin <i>in vitro</i> in mice islets and <i>in silico</i>. <b>Methods</b>: Size-matched pancreatic islets were divided into groups and incubated in the presence or absence of myricetin and agonists/antagonists of major insulin signaling pathways. The secreted insulin was measured by ELISA. Molecular docking studies were performed with the key player of insulin secretory pathways. <b>Results</b>: Myricetin dose-dependently enhanced insulin secretion in isolated mice islets, and its insulinotropic effect was exerted at high glucose concentrations distinctly different from glibenclamide. Myricetin-induced insulin secretion was significantly inhibited using the diazoxide. Furthermore, myricetin amplified glucose-induced insulin secretion in depolarized and glibenclamide-treated islets. Myricetin showed an additive effect with forskolin- and IBMX-induced insulin secretion. Interestingly, H89, a PKA inhibitor, and MAY0132, an Epac-2 inhibitor, significantly inhibited myricetin-induced insulin secretion. The <i>in silico</i> molecular docking studies further validated these <i>in vitro</i> findings in isolated pancreatic islets. <b>Conclusions</b>: Myricetin, a potential natural insulin secretagogue, amplifies glucose-induced insulin secretion <i>via</i> the cAMP-PKA-Epac-2 signaling pathway. |
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| ISSN: | 2227-9059 |