Activation of AMP-activated protein kinase by interleukin-6 in rat skeletal muscle: association with changes in cAMP, energy state, and endogenous fuel mobilization.
Activation of AMP-activated protein kinase by interleukin-6 in rat skeletal muscle: association with changes in cAMP, energy state, and endogenous fuel mobilization.
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DOI：
10.2337/db08-1293
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发表时间：
2009-09
期刊：
影响因子：
7.7
通讯作者：
Ruderman NB
中科院分区：
文献类型：
--
作者：
Kelly M;Gauthier MS;Saha AK;Ruderman NB
白细胞介素-6（IL-6）在体内和体外直接激活AMP活化蛋白激酶（AMPK）;然而，其机制尚不清楚。我们研究了这个问题，在骨骼肌使用孵育大鼠趾长伸肌（EDL）肌肉制备为工具。AMPK激活IL-6在时间上与EDL中AMP：ATP比率增加近三倍相一致。IL-6对AMPK活性和能量状态的影响被普萘洛尔抑制，表明β-肾上腺素能信号通路参与。与此观点一致，IL-6同时诱导cAMP的瞬时增加，其激活AMPK的能力被腺苷酸环化酶抑制剂2′5′-二脱氧腺苷阻断。此外，与其他β-肾上腺素能刺激一样，IL-6增加了EDL中的糖原分解和脂解。在体内C2 C12肌管和腓肠肌中观察到IL-6对AMPK、能量状态和cAMP含量的类似作用，表明它们不是孵育的EDL所独有的。这些研究表明，IL-6通过增加cAMP的浓度以及其次增加AMP：ATP比率来激活骨骼肌中的AMPK。他们还表明，IL-6浓度的大幅增加，例如运动期间肌肉合成的IL-6浓度，可能在骨骼肌内燃料储存的动员中发挥作用，作为恢复能量平衡的额外手段。
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. We examined this question in skeletal muscle using an incubated rat extensor digitorum longus (EDL) muscle preparation as a tool. 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 β-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 β-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. 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.
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影响因子：
4.1
作者：
Alam, N;Saggerson, ED
通讯作者：
Saggerson, ED
影响因子：
7.7
作者：
Febbraio, MA;Hiscock, N;Pedersen, BK
通讯作者：
Pedersen, BK
影响因子：
8.3
作者：
Gadonski, Giovani;Babbette, B.;Granger, Joey P.
通讯作者：
Granger, Joey P.
DOI：
10.1073/pnas.0705070104
发表时间：
2007-07-17
影响因子：
11.1
作者：
Jaeger, Sibylle;Handschin, Christoph;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
影响因子：
3.3
作者：
LO, S;RUSSELL, JC;TAYLOR, AW
通讯作者：
TAYLOR, AW