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论文题目: CLOCK and BMAL1 Regulate Muscle Insulin Sensitivity via SIRT1 in Male Mice
英文论文题目: CLOCK and BMAL1 Regulate Muscle Insulin Sensitivity via SIRT1 in Male Mice
第一作者: Liu, J; Zhou, B; Yan, MH; Huang, R; Wang, YG; He, ZS; Yang, YG; Dai, CG; Wang, YQ; Zhang, F; Zhai, QW
英文第一作者: Liu, J; Zhou, B; Yan, MH; Huang, R; Wang, YG; He, ZS; Yang, YG; Dai, CG; Wang, YQ; Zhang, F; Zhai, QW
联系作者: Zhai, QW (reprint author), Chinese Acad Sci, Key Lab Nutr & Metab, CAS Ctr Excellence Mol Cell Sci, Inst Nutr Sci,Shanghai Inst Biol Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
英文联系作者: Zhai, QW (reprint author), Chinese Acad Sci, Key Lab Nutr & Metab, CAS Ctr Excellence Mol Cell Sci, Inst Nutr Sci,Shanghai Inst Biol Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
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发表年度: 2016
卷: 157
期: 6
页码: 2259-2269
摘要: Circadian misalignment induces insulin resistance in both human and animal models, and skeletal muscle is the largest organ response to insulin. However, how circadian clock regulates muscle insulin sensitivity and the underlying molecular mechanisms are still largely unknown. Here we show circadian locomotor output cycles kaput (CLOCK) and brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein (BMAL)-1, two core circadian transcription factors, are down-regulated in insulin-resistant C2C12 myotubes and mouse skeletal muscle. Furthermore, insulin signaling is attenuated in the skeletal muscle of Clock(Delta 19/Delta 19) mice, and knockdown of CLOCK or BMAL1 by small interfering RNAs induces insulin resistance in C2C12 myotubes. Consistently, ectopic expression of CLOCK and BMAL1 improves insulin sensitivity in C2C12 myotubes. Moreover, CLOCK and BMAL1 regulate the expression of sirtuin 1 (SIRT1), an important regulator of insulin sensitivity, in C2C12 myotubes and mouse skeletal muscle, and two E-box elements in Sirt1 promoter are responsible for its CLOCK-and BMAL1-dependent transcription in muscle cells. Further studies show that CLOCK and BMAL1 regulate muscle insulin sensitivity through SIRT1. In addition, we find that BMAL1 and SIRT1 are decreased in the muscle of mice maintained in constant darkness, and resveratrol supplementation activates SIRT1 and improves insulin sensitivity. All these data demonstrate that CLOCK and BMAL1 regulate muscle insulin sensitivity via SIRT1, and activation of SIRT1 might be a potential valuable strategy to attenuate muscle insulin resistance related to circadian misalignment.
英文摘要: Circadian misalignment induces insulin resistance in both human and animal models, and skeletal muscle is the largest organ response to insulin. However, how circadian clock regulates muscle insulin sensitivity and the underlying molecular mechanisms are still largely unknown. Here we show circadian locomotor output cycles kaput (CLOCK) and brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein (BMAL)-1, two core circadian transcription factors, are down-regulated in insulin-resistant C2C12 myotubes and mouse skeletal muscle. Furthermore, insulin signaling is attenuated in the skeletal muscle of Clock(Delta 19/Delta 19) mice, and knockdown of CLOCK or BMAL1 by small interfering RNAs induces insulin resistance in C2C12 myotubes. Consistently, ectopic expression of CLOCK and BMAL1 improves insulin sensitivity in C2C12 myotubes. Moreover, CLOCK and BMAL1 regulate the expression of sirtuin 1 (SIRT1), an important regulator of insulin sensitivity, in C2C12 myotubes and mouse skeletal muscle, and two E-box elements in Sirt1 promoter are responsible for its CLOCK-and BMAL1-dependent transcription in muscle cells. Further studies show that CLOCK and BMAL1 regulate muscle insulin sensitivity through SIRT1. In addition, we find that BMAL1 and SIRT1 are decreased in the muscle of mice maintained in constant darkness, and resveratrol supplementation activates SIRT1 and improves insulin sensitivity. All these data demonstrate that CLOCK and BMAL1 regulate muscle insulin sensitivity via SIRT1, and activation of SIRT1 might be a potential valuable strategy to attenuate muscle insulin resistance related to circadian misalignment.
刊物名称: ENDOCRINOLOGY
英文刊物名称: ENDOCRINOLOGY
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学科: Endocrinology & Metabolism
英文学科: Endocrinology & Metabolism
影响因子: 4.286
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论文类别: Article
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