Isolation and identification of casein-derived dipeptidyl-peptidase 4 (DPP-4)-inhibitory peptide LPQNIPPL from gouda-type cheese and its effect on plasma glucose in rats

A water-soluble extract of a gouda-type cheese showed dipeptidyl-peptidase 4 (DPP-4)-inhibitory activity, which should improve glucose tolerance in type 2 diabetes. With liquid chromatography, we obtained four active fractions from the water-soluble extract and analysed the constituent peptides with liquid chromatography/mass spectrometry. Four peptides with the X–Pro-structure showed IC50 values of <200 μm. β-Casein peptide residues 70–77 (β-CN f70–77; LPQNIPPL) showed the highest DPP-4-inhibitory activity, which increased during the ripening period. Glucose tolerance tests were performed in rats orally administered synthesized LPQNIPPL (30 mg 100 g−1 rat weight) with a cross-over experimental design. The post-prandial area under the blood glucose curve was significantly reduced (P < 0.02) in the LPQNIPPL-administered group compared with that in the placebo-treated group. This is the first report that has identified DPP-4-inhibitory casein-derived peptides from gouda-type cheese with an effect on plasma glucose in a rat model.