The improvement in insulin sensitivity in skeletal muscle by coffee consumption is likely not due to the effects of caffeine, but rather due to other chemical components of coffee. Caffeine alone has been shown to decrease insulin sensitivity in humans [18] and interfere with insulin-stimulated glucose uptake and insulin signaling via inhibition of PI3-kinase and Akt [8] and [21]. It was also found that caffeine can also reduce insulin-independent glucose uptake in skeletal muscle [21], although others have shown that caffeine can stimulate this process via phosphorylation and activation of AMPK [7] and [14]. Although caffeine alone may have suppressing effects on insulin signaling, the other chemical components of coffee appears to negate this effect. Thus, caffeine alone and coffee containing caffeine exert differential effects on insulin signaling within skeletal muscle.