Egg White Ovotransferrin-Derived ACE Inhibitory Peptide Ameliorates Angiotensin II-Stimulated Insulin Resistance in Skeletal Muscle Cells

Scope: The renin-angiotensin system (RAS) is a major contributor to the development of insulin resistance and its related complications. Egg white ovotransferrin-derived tripeptides, IRW (Ile-Arg-Trp), IQW (Ile-Gln-Trp), or LKP (Leu-Lys-Pro) are previously identified as the inhibitors of angiotensin-converting enzyme (ACE), a key enzyme in the RAS. This study aims at determining whether these peptides are effective in improving insulin resistance, and their mechanisms of action, in a rat derived skeletal muscle cell line (L6 cells). Methods and results: Insulin resistance is induced by treating L6 cells with 1 m angiotensin II (Ang II) for 24 h. Effects of peptides on glucose uptake are determined using glucose uptake assay, glucose transporter 4 (GLUT4) translocation by immunofluorescence, reactive oxygen species (ROS) by dihydroethidium (DHE) staining, while insulin signaling pathway, Ang II receptor (AT1R or AT2R) levels, and NADPH oxidase activation are measured using Western Blot. Only IRW treatment significantly improves insulin resistance in L6 cells via stimulation of insulin signaling. IRW decreases Ang II-stimulated AT1R expression, ROS formation, and NADPH oxidase activation. Conclusions: Of three ACE inhibitory peptides studied, only IRW improves insulin resistance in L6 cells, at least partially via reduced AT1R expression and its anti-oxidative activity.