Evaluating in vitro dipeptidyl peptidase IV inhibition by peptides from common carp (Cyprinus carpio) roe in cell culture models

Dipeptidyl peptidase IV (DPP-IV) inhibitors have become a new choice to treat diabetes. Here, we studied the DPP-IV inhibitory activity of protein hydrolysates from common carp (Cyprinus carpio) roe. The molecular weight distribution and simulated gastrointestinal digestive stability of hydrolysates produced by four enzymes were analyzed. Papain-generated hydrolysate showed the highest DPP-IV inhibition and effective gastrointestinal stability. New effective peptide sequences from papain hydrolysates were identified using liquid chromatography-tandem mass spectrometry. The bioactivity of IPN-VAVD, which was identified from papain hydrolysate (IC50 value of 777.35 +/- 5.50 mu M), was investigated by Caco-2 and HepG2 cell models. We found that the DPP-IV inhibition by papain hydrolysate was not attenuated after simulated gastro-intestinal digestion. In addition, IPNVAVD significantly inhibited the DPP-IV secreted by Caco-2 cells with no cytotoxicity. It also promoted glucose uptake in insulin-resistant HepG2 cells. Transport experiments showed that IPNVAVD could be absorbed intactly by the Caco-2 cell monolayer. Protein hydrolysates from common carp roe inhibited DPP-IV effectively, and they may have potential as functional ingredients in food for diabetic patients.