Wheat Germ Peptide Ameliorates Hyperglycemia and Hyperlipidemia in Diabetic Rats through Modulation of SOCS3/IRS1/AKT and Lipid Metabolism Pathways.

Abstract

Type 2 diabetes mellitus (T2DM) is characterized by impaired glucose and lipid metabolism and remains a global health challenge due to limitations in current treatments. This study evaluated the effects of wheat germ peptide (WGP) on metabolic regulation and its underlying mechanisms in a T2DM rat model induced by a high-fat diet and streptozotocin. Post-WGP treatment, glucose consumption, glycogen content, hexokinase (HK) and pyruvate kinase (PK) activities, and lipid profiles were measured. Protein expression levels of SOCS3, IRS1, phosphorylated IRS1 (p-IRS1), Akt, phosphorylated Akt (p-Akt), GLUT2, GSK-3β, phosphorylated GSK-3β (p-GSK-3β), FOXO1, G6Pase, PEPCK, PPARα, SREBP1, ACC, phosphorylated ACC (p-ACC), and FAS were examined via Western blot analysis. Results demonstrated that WGP treatment significantly lowered plasma glucose, insulin levels, and the HOMA-IR index, while enhancing glucose consumption, glycogen synthesis, and activities of HK and PK. Furthermore, WGP alleviated hyperlipidemia. Western blot results showed reduced expression levels of SOCS3, FOXO1, PEPCK, G6Pase, and the p-IRS1/IRS1 ratio, alongside increased expression of GLUT2, p-Akt/Akt, and p-GSK-3β/GSK-3β ratios. WGP also elevated PPARα and p-ACC/ACC ratios while reducing SREBP1 and FAS expression levels. In conclusion, WGP enhances glucose metabolism via the SOCS3/IRS1/AKT signaling pathway and ameliorates hyperlipidemia by modulating lipid metabolism in diabetic rats.