In this study, the effect of two peptides, namely HL-7 and HL-10, on the percentage of cell death in L6 myoblast, proliferation, and metabolism of glucose in the INS-1 cell line, and the inhibitory role in the dipeptidyl peptidase IV (DPPIV) enzyme was investigated. The MTT assay was carried out to measure cell death and glucose metabolism in L6 myoblast and INS-1 cells, respectively. The analyses of glucose uptake in L6 myoblast and proliferation of INS-1 cells were performed in a culture medium containing 8 mM glucose and by the MTT kit, respectively. The inhibitory activity of two peptides against DPPIV was also conducted in-vitro and in-silico. Moreover, molecular docking and molecular dynamics simulations were done to estimate the stability and ability of HL-7 and HL-10 ligands in complex with the target enzyme. The results showed that both peptides had almost the same effects as the positive controls used in the two experiments on glucose uptake and cell proliferation (insulin and GABA, respectively). The glucose metabolism analysis showed an increase in insulin secretion in INS-1 cells treated with two peptides in a dose-dependent manner. The inhibitory assay experiments demonstrated that the IC50 values of peptides HL-7 and HL-10 for DPPIV were 17.04 and 18.75 µM, respectively. Also, in-vitro and in-silico results indicated the competitive behavior of the two peptides against the activity of DPPIV. Overall, it seems that the two peptides, HL-7, and HL-10 are able to increase insulin secretion by increasing the proliferation and of pancreatic beta cells and incretin-dependent pathways, such as the inhibition of the DPPIV enzyme.
