Evaluating the effects of IADHFL on inhibiting DPP-IV activity and expression in Caco-2 cells and contributing to the amount of insulin released from INS-1 cells in vitroElectronic supplementary information (ESI) available. See DOI: 10.1039/c7fo01950e

Dipeptidyl peptidase-IV (DPP-IV) is a serine exo -peptidase that can inactivate incretins by removing N-terminal dipeptides. Currently, inhibiting the DPP-IV activity is a common treatment for type 2 diabetes (T2D). The goal of this study is to investigate whether IADHFL, a novel DPP-IV inhibitory peptide identified from bighead carp ( Hypophthalmichthys nobilis ), has the potential to modulate T2D. IADHFL remained stable after simulated gastrointestinal digestion and significantly decreased the activity and expression of both soluble and membrane-bound DPP-IV after 24 h and 48 h of treatment. Intact peptide absorption was observed, but a percentage of the peptide was degraded while passing through a monolayer of Caco-2 cells. In addition, a double-layered cell model showed that the peptide could increase insulin secretion from INS-1 cells after glucose treatments of 2.8 mM and 16.7 mM. Finally, IADHFL could regulate the expression levels of genes associated with insulin secretion and T2D in INS-1 cells. Intact IADHFL was observed after simulated gastrointestinal digestion and part of the peptide was hydrolyzed into IADHF without reducing its DPP-IV inhibitory activity.