Amelioration of insulin resistance using the additive effect of ferulic acid and resveratrol on vesicle trafficking for skeletal muscle glucose metabolism.

Dysregulation of vesicle trafficking in muscle is one of the factors responsible for the pathogenesis of insulin resistance (IR). Ferulic acid (FER) and resveratrol (RSV) are known to have hypoglycemic property. In this study, differentiated L6 myotubes were induced with palmitate as a model of IR. Chemical ablation of muscle vesicles was used to investigate how FER and RSV influence glucose utilization. Results showed that both FER and RSV elicit glucose uptake and promote glycogen synthesis in insulin-resistant muscle cells. Mechanistic studies further showed that FER markedly enhances the transferrin receptor-containing endosomal compartment activities via phosphoinositide 3-kinase (PI3K)/atypical protein kinase C-dependent pathway, while RSV facilitates glucose transporter storage vesicles (GSV) trafficking via an exercise-like effect of conventional protein kinase C/5'-adenosine monophosphate-activated protein kinase (AMPK) modulation. Therefore, these two phenolic compounds promoted glucose transport through two separate routes, and they had an additive effect on the increase of glucose uptake in insulin-resistant muscle cells. These findings provide a basis for the understanding of the antidiabetic potential of RSV and FER combination.