Vaccinium ashei leaves extract alleviates insulin resistance via AMPK independent pathway in C2C12 myotube model

Blueberry (Vaccinium ashei) leaf has recently attracted attention as an anti-obesity food component. In this study, we examined the effects of blueberry leaf extract (BLEx) on insulin signaling in C2C12 differentiated myoblasts. The results showed that BLEx promotes the intracellular uptake of 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG) and phosphorylation of Akt under insulin stimulation. In addition, pretreatment with BLEx ameliorated TNF-alpha-nduced insulin resistance with regard to 2-NBDG uptake and Akt phosphorylation. Moreover, BLEx prevented the TNF-alpha-induced activation of JNK and NF-kB pathways and phosphorylation of IRS-1 at serine residue. BLEx failed to induce phosphorylation of AMPK as well as did not prevent the restoration of 2-NBDG uptake under TNF-alpha-induced insulin resistance. Overall, skeletal muscle is a putative target for the anti-diabetic effect of BLEx by amelioration of insulin resistance.