Dipeptidyl peptidase IV inhibitory properties of a whey protein hydrolysate: Influence of fractionation, stability to simulated gastrointestinal digestion and food-drug interaction

The invitro dipeptidyl peptidase IV (DPP-IV) inhibitory activity of a whey protein hydrolysate (WPH) generated with a food-grade pancreatic enzyme preparation was studied. The 50% inhibitory concentration (IC₅₀) value in the presence of WPH was 1.34±0.11mgmL^-1. Ultrafiltration (UF) fractionation of WPH allowed enrichment in DPP-IV inhibitory peptides. The permeates generated by UF through 5 and 2kDa membranes along with the hydrophilic fraction isolated by solid-phase extraction were significantly more potent DPP-IV inhibitors than WPH. Simulated gastrointestinal digestion of WPH resulted in an increased DPP-IV inhibitory potency (IC₅₀ value of 1.02±0.05mgmL^-1). Competitive inhibition of DPP-IV was observed with WPH and all its fractions, indicating a direct interaction of the bioactive peptides therein with the active site of DPP-IV. Combinations of sitagliptin, a conventional drug-inhibitor of DPP-IV, and whey-derived peptides resulted in an additive effect on DPP-IV inhibition.