Gastrointestinal stability of Dipeptidyl peptidase IV (DPP-IV)-inhibitory peptides identified in Tenebrio molitor
The use of insects recently emerged as an alternative source of high-quality protein for the obtention of peptides with a wide range of bioactivities, such as antidiabetic, while offering a more environmentally sustainable approach. However, antidiabetic DPP-IV inhibitory peptides are often rich in leucine, making them susceptible to degradation by pepsin and chymotrypsin during gastrointestinal digestion. This study uses bioinformatic prediction and in vitro activity assays to identify DPP-IV inhibitory peptides within the Tenebrio molitor proteome and assess their bioavailability. Conducting homology analysis, three peptides ‒ ILAP, FLQP, and APVAH ‒ were identified as complete matches, but efficient release of the sequences through targeted hydrolysis remains a significant challenge. Notably, a substantial decline in the DDP-IV inhibitory activity was found for the peptide fragments generated after digestion, compared to the original parent peptides. The inhibitory mechanisms of all three peptides were examined, revealing that mixed inhibition was associated with enhanced activity. Insect-derived peptides, such as APVAH with an IC50 of 0.013 ± 0.001 mg peptide/mL, may serve as effective DPP-IV inhibitors for diabetes management. However, protecting these peptides from gastrointestinal proteases is essential due to observed activity loss in digested fragments.
