Pea-derived peptides, VLP, LLP, VA, and LL, improve insulin resistance in HepG2 cells via activating IRS-1/PI3K/AKT and blocking ROS-mediated p38MAPK signaling.

This study evaluated the effect of four peptides, VLP, LLP, LL, and LL from pea on regulating glucose metabolism and antioxidant through IRS-1/PI3K/AKT and p38MAPK signal pathway in IR-HepG2 cell induced by 10-6 M insulin. The genes expression of PEPCK, G6Pase, GLUT2, and IRS-1 and proteins of IRS-1, p(Ser307)-IRS-1, AKT, p(Ser473)-AKT, p38MAPK, and p-p38MAPK were determined by RT-PCR and western blotting, respectively. Results show that they displayed highly potent on stimulation glucose metabolism and relief oxidative stress in IR-HepG2 cells. VLP, LLP, VA, and LL reduced Ser307 phosphorylation of IRS-1 and promoted Ser473 phosphorylation of AKT. Among them, LLP, VA, and LL increased the expression both gene and protein of GLUT2, and VLP and LL reduced p38MAPK phosphorylation showing strong antioxidant capacity. Therefore, pea oligopeptides have considerable potential for reversing the metabolic abnormalities associated with type 2 diabetes. PRACTICAL APPLICATIONS: This paper examined the intervention effect of VLP, LLP, VA, and LL that from pea on insulin resistance, and the mechanisms were detected by western blotting. The results provide a theoretical knowledge for the prevention of insulin resistance in T2D of pea-derived peptides and lay the foundation for the development of functional products and drugs in the future.