Whey proteins as source of dipeptidyl dipeptidase IV (dipeptidyl peptidase-4) inhibitors

Preclinical and clinical studies suggest that whey proteins can reduce postprandial glucose levels and stimulate insulin release in healthy subjects and in subjects with type 2 diabetes by reducing dipeptidyl peptidase-4 (DPP-4) activity in the proximal bowel and hence increasing intact incretin levels. Our aim was to identify DPP-4 inhibitors among short peptides occurring in hydrolysates of β-lactoglobulin, the major whey protein found in the milk of ruminants. We proved that the bioactive peptide Ile-Pro-Ala can be regarded as a moderate DPP-4 inhibitor.

Research highlights
► Whey proteins can reduce postprandial glucose levels and stimulate insulin release.
► Administration of whey protein was associated with higher levels of intact incretins.
► Dipeptidyl peptidase-4 (DPP-4) is the main enzyme responsible for incretin degradation.
► β-Lactoglobulin is the major whey protein found in the milk of cows and other ruminants.
► Ile-Pro-Ala (IPA) is a bioactive peptide generated by proteolysis of bovine β-lactoglobulin.
► Our results showed that IPA can be regarded as a moderate DPP-4 inhibitor.