Endocrine Abstracts

Preclinical and clinical studies suggest that whey protein intake can ameliorate postprandial glucose control and potentiate insulin release in both type-2 diabetic patients and healthy subjects.

Most likely, the insulinotropic effect of whey occurs by multiple pathways, including the potentiation of incretin activity through inhibition of DPP-4 in the proximal bowel, with the outcome of increasing intact incretin levels.

During last decades, it has been clearly shown that milk proteins, both caseins and whey proteins, are a source of short peptides with distinct biological activities which are generated by enzymatic hydrolysis during gastrointestinal digestion or during food processing.

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, by in silico and in vitro analysis.

The peptide Ile-Pro-Ala (IPA), called β-lactosin A have been previously identified in β-lactoglobulin hydrolysates prepared using proteinase K. We tested IPA in vitro for DPP-4 inhibitory activity, due to its structure similarity to the well-known inhibitor Ile-Pro-Ile. Although the substitution at position 3 resulted in a weakening of the inhibitory effect vs the reference compound Ile-Pro-Ile (IC₅₀ value of 59 vs 7 μM), our results showed that the β-lactoglobulin-derived peptide IPA can be regarded as a moderate DPP-4 inhibitor.

Two more peptides (Leu-Leu and Leu-Ala) proved to act as DPP-4 inhibitors but their potency was tenfold lower as compared with IPA.

Based on in silico analysis of published β-lactoglobulin amino acid sequences, the peptide IPA is conserved across bovine, ovine and caprine species and within bovine variants but it is absent in β-lactoglobulin from donkey. More interestingly, our results suggest that the differential level of expression of β-lactoglobulin across and within species could significantly affect DPP-4 inhibitor content of whey.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.