DPP-4 inhibitory and insulin-signaling-modulating potential of Allomyrina dichotoma larval protein hydrolysate

This study investigated the DPP-4 inhibitory and insulin signaling modulating activities of Allomyrina dichotoma (rhinoceros beetle) larval protein hydrolysate. Following enzymatic hydrolysis, three fractions were obtained by HPLC fractionation. Among them, fraction 3 (F3) exhibited the strongest dipeptidyl peptidase-4 (DPP-4) inhibitory activity (IC₅₀: 0.72 mg/mL). In an insulin-resistant HepG2 cell model, F3 significantly increased glucose uptake and enhanced Akt phosphorylation at Thr308, along with upregulation of GLUT4 expression, indicating improved insulin signaling responses. Furthermore, LC-MS/MS analysis identified 22 compounds enriched in hydrophobic and aromatic amino acids within F3. Molecular docking analysis predicted that these compounds interact with key DPP-4 active-site residues, including Glu205/Glu206, Tyr547, and Tyr662. Additionally, quantitative analysis revealed substantial levels of Trp, Val-Leu, and Met-Leu, which have previously been reported as DPP-4 inhibitory compounds. Collectively, these findings suggest that A. dichotoma larval hydrolysate contains bioactive peptides with DPP-4-inhibitory and insulin-signaling-modulating properties, supporting its potential for glucose homeostasis.