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

作者：Kelly Meghan; Gauthier Marie Soleil; Saha Asish K; Ruderman Neil B^*

来源：Diabetes, 2009, 58(9): 1953-1960.

DOI：10.2337/db08-1293

OBJECTIVE-Interleukin-6 (IL-6) directly activates AMP-activated 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 involvement of beta-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 2'5'-dideoxyadenosine. In addition, like other beta-adrenergic stimuli, IL-6 increased glycogen breakdown and lipolysis in the EDL. Similar effects of IL-6 on AMPK, energy state, and cAMP content were observed in C2C12 myotubes and gastrocnemius muscle in vivo, indicating that they were not unique to the incubated EDL.
CONCLUSIONS-These studies demonstrate that IL-6 activates AMPK in skeletal muscle by increasing the concentration of cAMP and, secondarily, the AMP:ATP ratio. They also suggest that substantial increases in IL-6 concentrations, such as those that can result from its synthesis by muscles during exercise, may play a role in the mobilization of fuel stores within skeletal muscle as an added means of restoring energy balance. Diabetes 58:1953-1960, 2009

• 出版日期2009-9