Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock

作者：Dyar Kenneth A^*; Ciciliot Stefano; Wright Lauren E; Bienso Rasmus S; Tagliazucchi Guidantonio M; Patel Vishal R; Forcato Mattia; Paz Marcia I P; Gudiksen Anders; Solagna Francesca; Albiero Mattia; Moretti Irene; Eckel Mahan Kristin L; Baldi Pierre; Sassone Corsi Paolo; Rizzuto Rosario; Bicciato Silvio; Pilegaard Henriette; Blaauw Bert; Schiaffino Stefano

来源：Molecular Metabolism, 2014, 3(1): 29-41.

DOI：10.1016/j.molmet.2013.10.005

• Bmal1
• Circadian rhythms
• Glucose metabolism
• Glucose uptake
• Skeletal muscle
• Muscle insulin resistance

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.

• 出版日期2014-2