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Characterization of DPP-IV Inhibitory Peptides Using an In Vitro Cell Culture Model of the Intestine

Ritian Jin,Jiaqi Shang,Xiangyu Teng,Ligang Zhang,Minhe Liao,Jiaxin Kang,Ran Meng,Dangfeng Wang,Haowei Ren,Ning Liu

Here, we characterize the activities of two depeptidyl peptidase-IV (DPP-IV) inhibitory peptides, VLATSGPG and LDKVFER, using the Caco-2 monolayer model for the intestine. VLATSGPG and LDKVFR inhibited the DPP-IV in the cells via a mixed-type inhibition mode, with in situ IC50 values of 207.3 and 148.5 μM, respectively. Furthermore, VLATSGPG and LDKVFR were transported intact across the cells, with Papp values of 2.41 ± 0.16 and 4.23 ± 0.29 × 10–7 cm/s, respectively. Fragmented peptides were identified in the basolateral side of the membrane. Two of these, GPG and VLA, exhibited high inhibitory activities of 83.6 ± 3.3 and 58.5 ± 2.5%, respectively, at 100 μM concentration. Although 3 mM VLATSGPG and LDKVFR were transported across the epithelium in a concentration-dependent manner, their transport did not damage the tight junction proteins, ZO-1 and occludin. This study demonstrates that the two peptides potentially regulate DPP-IV activity in the intestine.