Activation of AMP-Activated Protein Kinase by Interleukin-6 in Rat Skeletal Muscle Association With Changes in cAMP, Energy State, and

OBJECTIVE—Interleukin-6 (IL-6) directly activates AMP-acti-vated protein kinase (AMPK) in vivo and in vitro; however, the mechanism by which it does so is unknown. RESEARCH DESIGN AND METHODS—We examined this question in skeletal muscle using an incubated rat extensor digitorum longus (EDL) muscle preparation as a tool. RESULTS—AMPK activation by IL-6 coincided temporally with a nearly threefold increase in the AMP:ATP ratio in the EDL. The effects of IL-6 on both AMPK activity and energy state were inhibited by coincubation with propranolol, suggesting involve-ment of -adrenergic signaling. In keeping with this notion, IL-6 concurrently induced a transient increase in cAMP, and its ability to activate AMPK was blocked by the adenyl cyclase inhibitor 25-dideoxyadenosine. In addition, like other -adrenergic stim-uli, IL-6 increased glycogen breakdown and lipolysis in the EDL