Sturgeon protein-derived peptide KIWHHTF prevents insulin resistance via modulation of IRS-1/PI3K/AKT signaling pathways in HepG2 cells

Abstract

• KIWHHTF improved IR through stimulating IRS-1/PI3K/AKT signaling pathways. • Several key differential metabolites were identified. • Two key pathways were the most enriched. KIWHHTF, a sturgeon protein-derived peptide, has been demonstrated to have potent anti-inflammatory capacity in RAW264.7 macrophages. However, the influence of KIWHHTF on IR remains unclear. The aim of current study was therefore to investigate the effects of KIWHHTF on Insulin resistance (IR) and its underlying molecular mechanisms in HepG2 cells. Our results suggested that KIWHHTF increased the phosphorylation of IRS-1, PI3K, AKT, and the expression level of GLUT4, while down-regulated the phosphorylation of GS and the expression of PEPCK. In addition, metabolomics results suggested that differential metabolites include UDP-GlcNAc, DGA and 1-methyladenosine were increased after glucosamine treatment, but were reserved by KIWHHTF in IR HepG2 cells. Amino sugar and nucleotide metabolism and biosynthesis of unsaturated fatty acids were suggested as the most enriched pathways. Collectively, these results suggested that KIWHHTF improves the IR partly though IRS-1/PI3K/AKT signaling pathway. Moreover, UDP-GlcNAc, DGA and 1-methyladenosine were potential IR biomarker in HepG2 cells.