期刊
DIABETES
卷 62, 期 9, 页码 3081-3092出版社
AMER DIABETES ASSOC
DOI: 10.2337/db12-1261
关键词
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资金
- National Institutes of Health (NIH) [R01AR45670, R01DK68626]
- DERC at the Joslin Diabetes Center [P30DK036836]
- Weimann Foundation
- Beckett Foundation
- Danish National Research Foundation
- NIH [T32-DK-07260-29]
- Gettysburg College Professional Development grant
- Novo Nordisk Foundation Center for Basic Metabolic Research
- NNF Center for Basic Metabolic Research [Treebak Group] Funding Source: researchfish
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) 2-inactive transgenic 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 AMPK2-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.
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