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

• DOI: 10.1016/j.molmet.2013.10.005
• Publication Date: 2013-10-24T01:31:23Z
• Authors: Kenneth A. Dyar; Stefano Ciciliot; Lauren E. Wright; Rasmus S. Biensø; Guidantonio M. Ta...; Vishal R. Patel; Mattia Forcato; Marcia I.P. Paz; Anders Gudiksen; Francesca Solagna; Mattia Albiero; Irene Moretti; Kristin L. Eckel-...; Pierre Baldi; Paolo Sassone-Corsi; Rosario Rizzuto; Silvio Bicciato; Henriette Pilegaard; Bert Blaauw; Stefano Schiaffino
• Keywords: GLUT4; PDK4; Carbohydrate Metabolism

Circadian rhythms control metabolism and energy homeostasis, but the role of skeletal muscle clock has never been explored. We generated conditional inducible mouse lines with muscle-specific ablation core gene Bmal1. Skeletal muscles from these mice showed impaired insulin-stimulated glucose uptake reduced protein levels GLUT4, insulin-dependent transporter, TBC1D1, a Rab-GTPase involved in GLUT4 translocation. Pyruvate dehydrogenase (PDH) activity was also due to altered expression circadian genes Pdk4 Pdp1, coding for PDH kinase phosphatase, respectively. inhibition leads oxidation diversion glycolytic intermediates alternative metabolic pathways, as revealed by metabolome analysis. The induced Bmal1 knockout suggests that major physiological is prepare transition rest/fasting phase active/feeding phase, when becomes predominant fuel muscle.