Transport, Stability, and In Vivo Hypoglycemic Effect of a Broccoli-Derived DPP-IV Inhibitory Peptide VPLVM

Diabetes is a major metabolic disease that requires long-term pharmacotherapy. Bioactive peptides have unique advantages such as higher potency, selectivity, and safety over small molecules and have achieved great success in the treatment of diabetes. We previously isolated a dipeptidyl peptidase-IV (DPP-IV) inhibitory peptide VPLVM with IC50 = 99.68 μM from the protein hydrolysates of broccoli stems and leaves. Here, we evaluated the interaction with DPP-IV, transport, stability, and in vivo hypoglycemic effects of VPLVM. VPLVM interacted closely and steadily with DPP-IV at S1 and S2 pockets. VPLVM had a good gastrointestinal enzyme resistance and was transported through the Caco-2 cell monolayer via paracellular diffusion and by the PepT1 with a Papp of 6.96 × 10–7 cm/s. VPLVM has a t1/2 of 12.56 ± 0.41 min in vitro plasma stability. In the oral glucose tolerance test, VPLVM showed an excellent hypoglycemic effect at 30 min after administration. VPLVM has potential as a candidate for the treatment of hyperglycemia.