Authors: HuiYoung Lee Arijeet K Gattu JoãoPaulo G Camporez Shoichi Kanda Blas Guigni Mario Kahn Dongyan Zhang Thomas Galbo Andreas L Birkenfeld Francois R Jornayvaz Michael J Jurczak Cheol Soo Choi Zhen Yan R Sanders Williams Gerald I Shulman Varman T Samuel
Publish Date: 2014/04/11
Volume: 57, Issue: 6, Pages: 1232-1241
Abstract
Aerobic exercise increases muscle glucose and improves insulin action through numerous pathways including activation of Ca2+/calmodulindependent protein kinases CAMKs and peroxisome proliferator γ coactivator 1α PGC1α While overexpression of PGC1α increases muscle mitochondrial content and oxidative type I fibres it does not improve insulin action Activation of CAMK4 also increases the content of type I muscle fibres PGC1α level and mitochondrial content However it remains unknown whether CAMK4 activation improves insulin action on glucose metabolism in vivoThe effects of CAMK4 activation on skeletal muscle insulin action were quantified using transgenic mice with a truncated and constitutively active form of CAMK4 CAMK4● in skeletal muscle Tissuespecific insulin sensitivity was assessed in vivo using a hyperinsulinaemic–euglycaemic clamp and isotopic measurements of glucose metabolismThe rate of insulinstimulated wholebody glucose uptake was increased by ∼25 in CAMK4● mice This was largely attributed to an increase of ∼60 in insulinstimulated glucose uptake in the quadriceps the largest hindlimb muscle These changes were associated with improvements in insulin signalling as reflected by increased phosphorylation of Akt and its substrates and an increase in the level of GLUT4 protein In addition there were extramuscular effects CAMK4● mice had improved hepatic and adipose insulin action These pleiotropic effects were associated with increased levels of PGC1αrelated myokines in CAMK4● skeletal muscle
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