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Diabetes. 2009 Sep;58(9):1953-60. doi: 10.2337/db08-1293. Epub 2009 Jun 5.

Activation of AMP-activated protein kinase by interleukin-6 in rat skeletal muscle: association with changes in cAMP, energy state, and endogenous fuel mobilization.

Author information

1
Department of Medicine, Section of Endocrinology, Diabetes Research Unit, Boston University School of Medicine, Boston, Massachusetts, USA.

Abstract

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.

PMID:
19502419
PMCID:
PMC2731526
DOI:
10.2337/db08-1293
[Indexed for MEDLINE]
Free PMC Article

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