Activation of AMP-activated protein kinase by interleukin-6 in rat skeletal muscle: association with changes in cAMP, energy state, and endogenous fuel mobilization.
Level 5 - mechanism / opinion, no new human data
Preclinical animal (rat) and in vitro (C2C12 cell line) mechanistic laboratory study.
PubMed 19502419 · doi:10.2337/db08-1293
What was done
The authors examined how interleukin-6 (IL-6) activates AMP-activated protein kinase (AMPK) in skeletal muscle. They tested incubated rat extensor digitorum longus (EDL) muscles, cultured C2C12 myotubes, and rat gastrocnemius muscle in vivo. To assess beta-adrenergic and cyclic AMP (cAMP) signaling pathways, muscle preparations were treated with IL-6 alongside pharmacological inhibitors, including propranolol (beta-blocker) and 2'5'-dideoxyadenosine (adenylate cyclase inhibitor), while tracking cAMP levels, AMP:ATP ratio, glycogen breakdown, and lipolysis.
What was found
IL-6-induced AMPK activation in rat EDL coincided temporally with a nearly threefold increase in the AMP:ATP ratio. Propranolol inhibited IL-6-mediated AMPK activity and the shift in energy state. IL-6 elicited a transient rise in cAMP, and the adenylate cyclase inhibitor 2'5'-dideoxyadenosine blocked IL-6's ability to activate AMPK. IL-6 also increased glycogen breakdown and lipolysis in EDL muscle. Similar effects on AMPK, energy state, and cAMP were observed in C2C12 myotubes and gastrocnemius muscle in vivo. Specific numerical values beyond the threefold ratio increase were not reported in the abstract.
Why it matters
This study outlines a mechanistic pathway connecting muscle-derived IL-6 to cAMP signaling, altered AMP:ATP balance, and AMPK activation, illustrating how IL-6 during exercise may facilitate endogenous fuel mobilization.
Limits
The findings are derived entirely from rodent tissue and cell culture models, limiting direct translation to human physiology. The abstract omits sample sizes (n), exact dosages, quantitative metabolic rates, and statistical dispersion metrics.
Cited by
- supports Interleukin-6 activates AMP-activated protein kinase (AMPK) during or following exercise.