How DPP-IV Inhibiting Peptides Are Released from Fish Collagen During Digestion

ProteaC-digested collagen hydrolysate showed the highest DPP-IV inhibitory activity with an IC50 of 0.58 ± 0.02 mg/mL. The enzyme preferentially cleaved at glycine and hydrophobic amino acid residues at the P1' position and showed strong preference for hydroxyproline at the P1 position. Large amounts of Gly-Pro-type peptides consisting of 4, 6, and 9 amino acids were released. The dynamic release followed a clear pattern: precursor peptides → target active peptides → shorter peptides.

Researchers used tilapia skin collagen as a starting material and tested multiple proteases to determine which released the most potent DPP-IV inhibitory peptides. They analyzed cleavage selectivity of each enzyme and tracked the dynamic release mechanism of Gly-Pro-type peptides over the course of digestion. DPP-IV inhibitory activity was measured using IC50 values.

DPP-IV inhibitors are a major class of diabetes medications. Understanding how natural DPP-IV inhibitory peptides are released from food proteins like collagen could lead to functional foods or nutraceuticals that help manage blood sugar. This study provides the mechanistic blueprint for optimizing that release process.

There is growing interest in food-derived bioactive peptides as natural alternatives or complements to pharmaceutical DPP-IV inhibitors for blood sugar management. This work advances the understanding of how to efficiently produce these peptides from an abundant and sustainable source — fish processing waste. It bridges food science and peptide therapeutics.

This is an in vitro biochemistry study — the DPP-IV inhibitory activity was measured in a test tube, not in living organisms. Whether these peptides survive further digestion in the human gut, get absorbed intact, and reach effective concentrations in the bloodstream is unknown. The IC50 value represents enzyme inhibition in isolation, not a clinical blood sugar effect.