Lowering of Blood Glucose Levels with the Peptide Mixture Deglusterol in In Vitro and In Vivo Models

This study aimed to investigate the blood glucose-lowering effect of the peptide complex Deglusterol, which was isolated from corn extract, in insulin-resistance models. It was found to inhibit insulin receptor substrate (IRS) Ser302 phosphorylation, known as the insulin resistance mechanism, through the inhibition of tumor necrosis factor-α (TNF-α) signaling and the induction of AMP-activated protein kinase phosphorylation. Furthermore, the phosphorylation of IRS Tyr632, phosphoinositide 3-kinase (PI3K), and AKT that is involved in the insulin action mechanism was decreased by TNF-α, whereas Deglusterol increased their phosphorylations, leading to an increase of glucose uptake rate by 190% through glucose transporter type 4 (GLUT4) compared with TNF-α-treated group in C2C12 cells. In addition to insulin signaling activation, Deglusterol treatment resulted in significantly greater mRNA expressions of IRS (190%) and GLUT4 (140%) as well as that of leptin (260%) and adiponectin (140%), which are indicators of insulin sensitivity. In animal models with type 2 diabetes, the blood glucose concentrations in the Deglusterol-administered group were significantly reduced by 50% compared with the control group. Deglusterol suppressed insulin resistance and restored insulin sensitivity, which contributed to lowering blood glucose concentrations in the insulin-resistant models, suggesting its potential as a blood glucose-lowering agent for people at high risk of type 2 diabetes or prediabetes.