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

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.

Automated summary

The study found that KIWHHTF can improve insulin resistance through the IRS-1/PI3K/AKT signaling pathway, and it can also affect the levels of metabolites, among which UDP-GlcNAc, DGA and 1-methyladenosine are potential biomarkers for IR.