Hypoglycemic Effect of Hydrophobic BCAA Peptides Is Associated with Altered PI3K/Akt Protein Expression

The hypoglycemic activities of the hydrophobic branched-chain amino acid (BCAA) peptides from seabuckthorn seed protein were preliminarily characterized in type 2 diabetic db/db mice. Four novel BCAA peptides (18.27 ± 0.26% (w/w): Leu/Ile-Pro-Glu-Asp-Pro, Asp-Leu/Ile-Val-Gly-Glu, Leu/Ile-Pro, and Leu/Ile-Pro-Leu/Ile) were identified in seabuckthorn seed protein. The protein content in seabuckthorn seed protein hydrolysate, obtained using 80% ethanol, was 78.8 ± 1.4% (w/w). Animal experiments revealed that oral administration of BCAA peptides (all four) significantly reversed the diabetic symptoms. Compared to the db/db group (control), body weight and insulin resistance were ameliorated after treatment with BCAA peptides (0.5, 1.0, 2.0 mg/(g d)). Also, the treatment remarkably reduced the fasting blood glucose (FBG) levels by upregulation of glucose transporter 4 (GULT4). Moreover, BCAA peptides significantly increased the muscle glycogen content (22.6 ± 0.9 nmol/mg) via the downregulation of protein kinase B (AKT) and glycogen synthase kinase-3β (GSK-3β) while increasing the activity of glycogen synthase (GS). BCAA peptides also significantly upregulated the protein levels of phosphatidylinositol 3-kinase (PI3K). We show that BCAA peptides alleviated insulin resistance associated with altered PI3K/Akt protein expression in the skeletal muscle of db/db mice.