Fish Roe Polypeptide Exerts Hypoglycemia Activity via Regulating Insulin Secretion Mediated by Nrf2/ERK Signaling

In recent years, marine-derived bioactive peptides have gained considerable attention owing to their high biomedical and pharmaceutical potential. In this study, we investigated the hypoglycemic activity of fish roe polypeptide (FRP) in islet beta-cells (INS-1) and the molecular mechanism whereby FRP exerts this effect. Insulin secretion, cell viability, cell apoptosis, intracellular reactive oxygen species (ROS), and intracellular antioxidant-related enzymes were detected. The nuclear factor erythroid 2-related factor 2 (Nrf2)/extracellular signal-regulated kinase (ERK) pathway was analyzed to reveal the mechanism underpinning FRP's hypoglycemic effect. The results showed that FRP treatment promoted insulin secretion and cell viability, reduced apoptosis and intracellular ROS levels, and increased the activity and content of antioxidant-related enzymes. Cell signaling pathway analysis revealed that FRP was able to alleviate H2O2-induced oxidative stress by activating the Nrf2/ERK pathway. This was demonstrated by an evident decrease in cell viability and insulin secretion in the presence of the ERK blocker U0126. Altogether, these results suggest that FRP exerts its hypoglycemic effect by regulating insulin secretion, which is mediated by Nrf2/ERK signaling.

Automated summary

The study showed that fish roe polypeptide (FRP) can promote insulin secretion and cell viability, reduce apoptosis and intracellular ROS levels, and increase the activity and content of antioxidant-related enzymes by activating the Nrf2/ERK pathway, thus exerting its hypoglycemic effect.