The effect of exercise induced cytokines on insulin stimulated glucose transport in C2C12 cells

Skeletal muscle contractile activity increases the production of the myokines interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-15 (IL-15) and also skeletal muscle glucose transport. Previous work has revealed a role for IL-6 in mediating glucose uptake, while research on the physiological roles of IL-8 and IL-15 is not so abundant. In the present study we investigated the effects of different concentrations and combinations of IL-6, IL-8 and IL-15 on insulin stimulated glucose transport in C2C12 cells. Furthermore, we also measured AMPK Thr172 and Akt Ser473 phosphorylation via Western blotting. Exposure to 20 pg/ml of individual cytokines had no affect on glucose transport while 1 ng/ml enhanced (P < 0.05) glucose uptake with IL-6, IL-8 and IL-15, respectively. Moreover, the combinations of IL-8 + IL-6 and IL-15 + IL-6 at both 20 pg/ml and 1 ng/ml stimulated (P < 0.05) glucose transport with IL-8 + IL-15 and IL-8 + IL-6 + IL-15 only increasing (P < 0.05) glucose transport at 1 ng/ml, with no affect observed of these combinations at 20 pg/ml. The changes in glucose transport were all associated with an increase (P < 0.05) in AMPK Thr172 phosphorylation with no changes in Akt Ser473 phosphorylation. These findings demonstrated that the exercise induced myokines IL-6, IL-8 and IL-15 enhance glucose transport at 1 ng/ml, with changes only seen at 20 pg/ml with certain myokine combinations. Furthermore these changes in insulin stimulated glucose transport were associated with increased AMPK phosphorylation.

► Only individual cytokines at concentrations of 1 ng/ml stimulate skeletal muscle glucose transport. ► At 20 pg/ml combined cytokines (IL-8 + IL-6 and IL-6 + IL-15) stimulate glucose transport. ► All combinations of cytokines at 1 ng/ml increase glucose transport. ► Changes in glucose transport were associated with increased AMPK phosphorylation.