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

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.