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- Title
Contraction and AICAR Stimulate IL-6 Vesicle Depletion From Skeletal Muscle Fibers In Vivo.
- Authors
Lauritzen, Hans P. M. M.; Brandauer, Josef; Schjerling, Peter; Ho-Jin Koh; Treebak, Jonas T.; Hirshman, Michael F.; Galbo, Henrik; Goodyear, Laurie J.
- Abstract
Recent studies suggest that interleukin 6 (IL-6) is released from contracting skeletal muscles; however, the cellular origin, secretion kinetics, and signaling mechanisms regulating IL-6 secretion are unknown. To address these questions, we developed imaging methodology to study IL-6 in fixed mouse muscle fibers and in live animals in vivo. Using confocal imaging to visualize endogenous IL-6 protein in fixed muscle fibers, we found IL-6 in small vesicle structures distributed throughout the fibers under basal (resting) conditions. To determine the kinetics of IL-6 secretion, intact quadriceps muscles were transfected with enhanced green fluorescent protein (EGFP)-tagged IL-6 (IL-6-EGFP), and 5 days later anesthetized mice were imaged before and after muscle contractions in situ. Contractions decreased IL-6-EGFP--containing vesicles and protein by 62% (P, 0.05), occurring rapidly and progressively over 25 min of contraction. However, contraction-mediated IL-6-EGFP reduction was normal in muscle-specific AMP-activated protein kinase (AMPK)α2-inactive transgenic a mice. In contrast, the AMPK activator AICAR decreased IL-6-EGFP vesicles, an effect that was inhibited in the transgenic mice. In conclusion, resting skeletal muscles contain IL-6--positive vesicles that are expressed throughout myofibers. Contractions stimulate the rapid reduction of IL-6 in myofibers, occurring through an AMPKα2-independent mechanism. This novel imaging methodology clearly establishes IL-6 as a contraction-stimulated myokine and can be used to characterize the secretion kinetics of other putative myokines.
- Subjects
INTERLEUKIN-6; SKELETAL muscle; VESICLES (Cytology); SECRETION; PROTEIN kinases; IMAGING systems
- Publication
Diabetes, 2013, Vol 62, Issue 9, p3081
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db12-1261