Ferulic acid improves palmitate-induced insulin resistance by regulating IRS-1/Akt and AMPK pathways in L6 skeletal muscle cells.

Abstract

Objective: Increased plasma-free fatty acid (FFA) induced by obesity can trigger insulin resistance and it is a significantly dangerous constituent in the progression of diabetes. Although ferulic acid has various physiological functions, no studies have examined ferulic acid's effects on insulin-resistant muscle cells. This study investigated the effect of ferulic acid on improving palmitic acid-induced insulin resistance in L6 skeletal muscle cells.

Methods: Palmitic acid induces insulin resistance by inhibiting the phosphorylation of IRS-1_tyr and stimulating the phosphorylation of IRS-1_ser in diabetes. Thus, palmitic acid (0.75 mM) was used as an insulin resistance inducer and ferulic acid was treated at various concentrations (2, 5, 10, and 20 uM) in L6 skeletal muscle cells.

Results: Palmitic acid significantly reduced the cell viability of L6 skeletal muscle cells, whereas ferulic acid treatment significantly increased cell viability in a concentration-dependent manner. Palmitic acid significantly reduced glucose uptake due to insulin resistance in the muscle cells; however, ferulic acid treatment remarkably increased glucose uptake. Ferulic acid promoted the phosphorylation of IRS-1_tyr that palmitic acid inhibited, while also suppressing the palmitic acid-induced phosphorylation of IRS-1_ser. Ferulic acid activated PI3K and then stimulated the phosphorylation of Akt, which increased PM-GLUT4 expression, thereby stimulating glucose uptake into insulin-resistant muscle cells. Ferulic acid also increased glycogen synthesis by phosphorylating GSK3β via the Akt pathway. Additionally, ferulic acid significantly promoted phosphorylation of AMPK, enhancing PM-GLUT4 levels and glucose uptake.

Conclusions: These results suggest that ferulic acid may improve palmitate-induced insulin resistance by regulating IRS-1/ Akt and the AMPK pathway in L6 skeletal muscle cells.