Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock.
Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock.
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DOI：
10.1016/j.molmet.2013.10.005
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发表时间：
2014-02
影响因子：
8.1
通讯作者：
Schiaffino S
中科院分区：
文献类型：
--
作者：
Dyar KA;Ciciliot S;Wright LE;Biensø RS;Tagliazucchi GM;Patel VR;Forcato M;Paz MI;Gudiksen A;Solagna F;Albiero M;Moretti I;Eckel-Mahan KL;Baldi P;Sassone-Corsi P;Rizzuto R;Bicciato S;Pilegaard H;Blaauw B;Schiaffino S
昼夜节律控制新陈代谢和能量平衡，但骨骼肌时钟的作用从未被探索过。我们产生了有条件的和可诱导的小鼠品系与肌肉特异性消融的核心时钟基因Bmal 1。这些小鼠的骨骼肌显示胰岛素刺激的葡萄糖摄取受损，GLUT 4（胰岛素依赖性葡萄糖转运蛋白）和TBC 1D 1（一种参与GLUT 4易位的Rab-GT3）的蛋白水平降低。丙酮酸脱氢酶（PDH）的活性也降低，由于昼夜节律基因Pdk 4和Pdp 1的表达改变，分别编码PDH激酶和磷酸酶。如代谢组学分析所示，PDH抑制导致葡萄糖氧化减少和糖酵解中间体转向替代代谢途径。由肌肉特异性Bmal 1敲除诱导的葡萄糖代谢受损表明，肌肉时钟的主要生理作用是准备从休息/禁食阶段过渡到活动/进食阶段，此时葡萄糖成为骨骼肌的主要燃料。
Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-stimulated glucose uptake with reduced protein levels of GLUT4, the insulin-dependent glucose transporter, and TBC1D1, a Rab-GTPase involved in GLUT4 translocation. Pyruvate dehydrogenase (PDH) activity was also reduced due to altered expression of circadian genes Pdk4 and Pdp1, coding for PDH kinase and phosphatase, respectively. PDH inhibition leads to reduced glucose oxidation and diversion of glycolytic intermediates to alternative metabolic pathways, as revealed by metabolome analysis. The impaired glucose metabolism induced by muscle-specific Bmal1 knockout suggests that a major physiological role of the muscle clock is to prepare for the transition from the rest/fasting phase to the active/feeding phase, when glucose becomes the predominant fuel for skeletal muscle.
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DOI：
10.1073/pnas.1118726109
发表时间：
2012-04-03
影响因子：
11.1
作者：
Eckel-Mahan, Kristin L.;Patel, Vishal R.;Sassone-Corsi, Paolo
通讯作者：
Sassone-Corsi, Paolo
DOI：
10.1073/pnas.1014523107
发表时间：
2010-11-02
影响因子：
11.1
作者：
Andrews, Jessica L.;Zhang, Xiping;Esser, Karyn A.
通讯作者：
Esser, Karyn A.
影响因子：
7.7
作者：
An D;Toyoda T;Taylor EB;Yu H;Fujii N;Hirshman MF;Goodyear LJ
通讯作者：
Goodyear LJ
影响因子：
16
作者：
Bruning, JC;Michael, MD;Kahn, CR
通讯作者：
Kahn, CR
影响因子：
7.7
作者：
Høeg LD;Sjøberg KA;Jeppesen J;Jensen TE;Frøsig C;Birk JB;Bisiani B;Hiscock N;Pilegaard H;Wojtaszewski JF;Richter EA;Kiens B
通讯作者：
Kiens B