Preparation, identification, activity prediction, and protective effects on IR-HepG2 cells of five novel DPP-IV inhibitory peptides from protein hydrolysate of skipjack tuna dark muscles

values of 42.46 ± 5.02, 37.71 ± 9.17, 58.85 ± 14.42, 49.94 ± 6.69 and 57.15 ± 6.13 μM, respectively) were screened from the protein hydrolysate. The above five peptides were proved to effectively promote glucose consumption in the insulin resistant-HepG2 (IR-HepG2) cell model considering that the glucose consumption rates of APP, PPP, DPLL, EAVP and EAIP treatment groups are all more than twice that of the dexamethasone group. Accordingly, mechanistic studies showed that these peptides interacted with PI3K/AKT and AMPK signaling pathways and promoted the phosphorylation of PI3K p110, AKT and AMPK (the protein expressions of PI3K p110, p-AKT and p-AMPK in APP, PPP, DPLL, EAVP and EAIP treatment groups are 1.64-2.22 fold compared with that in the dexamethasone group), thereby enhancing glucose uptake and further alleviating insulin resistance. These findings demonstrated that skipjack tuna dark muscle is a potential DPP-IV inhibitory peptide source, and five DPP-IV inhibitory peptides from its hydrolysate may exert potent anti-diabetic activity. In comparison, PPP may be the most potential active ingredient for healthy food against type 2 diabetes mellitus in the five screened peptides considering synthetically the DPP-IV inhibitory rate, bioavailability and synthesis cost.