Blue mussel peptides treat diabetes through DPP-IV inhibition, GLP-1 increase, and anti-inflammatory effects in mice | Research

The takeaway

Two bioactive peptides from blue mussel (PIISVYWK and FSVVPSPK) improved glycemic control in diabetic mice through multi-target mechanisms: DPP-IV and α-glucosidase inhibition, GLP-1 increase, NF-κB suppression, and pancreatic β-cell protection.

Multi-target at 1-10 mg/kg
Two mussel peptides achieved multi-mechanism diabetes treatment (DPP-IV, GLP-1, anti-inflammatory, antioxidant, β-cell protection) at doses 20-200x lower than metformin

What the researchers found

P1 and P2: inhibited α-glucosidase and DPP-IV in Caco-2 cells. ↑GLP-1 levels. ↓NF-κB, IL-6, TNF-α, IL-1β. ↑SOD, GPx, CAT. Preserved β-cell function. ↑insulin, regulated glucagon. 1-10 mg/kg vs metformin 200 mg/kg in HFD/STZ mice.

Why it matters

Marine-derived peptides that simultaneously target multiple diabetes mechanisms could become natural therapeutic alternatives or adjuncts to existing drugs, with potentially fewer side effects.

How the study worked

In vitro: Caco-2 cell DPP-IV, α-glucosidase, glucose uptake, SGLT-1/GLUT2 expression. In vivo: HFD/STZ diabetic mice, P1/P2 (1 or 10 mg/kg) or metformin (200 mg/kg) for 4 weeks.

What this study cannot tell us

Mouse study. Bioavailability of oral peptides in humans uncertain. Short treatment (4 weeks). Dose comparison to metformin may not be directly translatable.

How to read the evidence

Preclinical with in vitro and in vivo validation. Comprehensive mechanism characterization.

When this study was published

Published in 2025.

The bigger picture

Natural DPP-IV inhibitory peptides from food sources could complement pharmaceutical approaches. These mussel peptides essentially replicate multiple diabetes drug mechanisms in a single natural compound.

Questions still open

Could these peptides survive human digestion to reach therapeutic targets?
Would mussel protein consumption provide sufficient peptide for glycemic benefit?
Can these peptides be combined with existing diabetes drugs?

Common questions

Can mussel proteins help with diabetes?

In this study, two specific peptides from blue mussel improved blood sugar control in diabetic mice through multiple mechanisms: blocking enzymes that raise blood sugar, boosting the protective hormone GLP-1, reducing inflammation, and protecting insulin-producing cells. These effects worked at very low doses.

How do these peptides compare to diabetes drugs?

Remarkably, at 1-10 mg/kg, these peptides achieved effects similar to metformin at 200 mg/kg by targeting multiple pathways simultaneously—including the same DPP-IV enzyme that sitagliptin (Januvia) blocks, and GLP-1 enhancement like semaglutide. However, this is from a mouse study and human translation is not yet confirmed.

Read the original research

Bioactive peptides PIISVYWK and FSVVPSPK improve glucose homeostasis by targeting DPP-IV and glucose transport in type 2 diabetic mice.

International immunopharmacology, 158, 114844

View on PubMed ↗Publisher’s paper ↗

Citation

Suryaningtyas, Indyaswan T; Jung, Won-Kyo; Lee, Sei-Jung; Je, Jae-Young. (2025). Bioactive peptides PIISVYWK and FSVVPSPK improve glucose homeostasis by targeting DPP-IV and glucose transport in type 2 diabetic mice.. International immunopharmacology, 158, 114844. https://doi.org/10.1016/j.intimp.2025.114844