Oligopeptides (Thr–His–Leu–Pro–Lys
(THLPK), His–Pro–Leu–Lys (HPLK), Leu–Pro–Lys
(LPK), His–Leu–Lys (HLK), and Leu–His–Lys
(LHK)) are newly identified from rapeseed napin (Brassica
napus) protein-derived hydrolysates with the capability
of upregulating glucose transporter-4 (GLUT4) expression and translocation.
However, whether each of them enhances GLUT4 expression and translocation
and their specific mechanisms remain unclear. Here, we assess the
effects of the oligopeptides against insulin resistance (IR) and oxidative
stress in hepatocytes and screen out the most antidiabetic one. Specifically,
compared with other oligopeptides, LPK not only remarkably elevated
glucose consumption to 8.45 mmol/L protein; superoxide dismutase (SOD)
activity to 319 U/mg protein; GLUT4 expression and translocation;
and phosphorylated level of insulin receptor substrate-1 (IRS-1),
phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) (P < 0.05) but also remarkably attenuated the reactive
oxygen species (ROS) level to 2255, lactate dehydrogenase (LDH) activity
to 20.5 U/mg protein, malondialdehyde (MDA) content to 241 nmol/mg
protein, and NO content to 1302 μmol/mL protein (P < 0.05). These findings demonstrated that antidiabetic oligopeptide
LPK possessed the most potential to protect HepG2 cells from IR and
oxidative stress via activating IRS-1/PI3K/Akt/GLUT4 and regulating
common oxidative markers in vitro.