Enhanced muscle insulin sensitivity after contraction/exercise is mediated by AMPK
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Enhanced muscle insulin sensitivity after contraction/exercise is mediated by AMPK. / Kjøbsted, Rasmus; Munk-Hansen, Nanna; Birk, Jesper Bratz; Foretz, Marc; Viollet, Benoit; Björnholm, Marie; Zierath, Juleen R; Treebak, Jonas Thue; Wojtaszewski, Jørgen.
I: Diabetes, Bind 66, Nr. 3, 2017, s. 598-612.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Enhanced muscle insulin sensitivity after contraction/exercise is mediated by AMPK
AU - Kjøbsted, Rasmus
AU - Munk-Hansen, Nanna
AU - Birk, Jesper Bratz
AU - Foretz, Marc
AU - Viollet, Benoit
AU - Björnholm, Marie
AU - Zierath, Juleen R
AU - Treebak, Jonas Thue
AU - Wojtaszewski, Jørgen
N1 - CURIS 2017 NEXS 073
PY - 2017
Y1 - 2017
N2 - Earlier studies have demonstrated that muscle insulin sensitivity to stimulate glucose uptake is enhanced several hours after an acute bout of exercise. Using 5-aminoimidazole-4-carboxamide-ribonucleotide (AICAR), we recently demonstrated that prior activation of AMPK is sufficient to increase insulin sensitivity in mouse skeletal muscle. Here we aimed to determine whether activation of AMPK is also a prerequisite for the ability of muscle contraction to increase insulin sensitivity. We found that prior in situ contraction of m. extensor digitorum longus (EDL) and treadmill exercise increased muscle and whole body insulin sensitivity in wild type (WT) mice, respectively. These effects were not found in AMPKα1α2 muscle-specific knockout mice. Prior in situ contraction did not increase insulin sensitivity in m. soleus from either genotype. Improvement in muscle insulin sensitivity was not associated with enhanced glycogen synthase activity or proximal insulin signaling. However, in WT EDL muscle prior in situ contraction enhanced insulin-stimulated phosphorylation of TBC1D4 Thr(649) and Ser(711) Such findings are also evident in prior exercised and insulin sensitized human skeletal muscle. Collectively, our data suggest that the AMPK-TBC1D4 signaling axis is likely mediating the improved muscle insulin sensitivity after contraction/exercise and illuminates an important and physiological relevant role of AMPK in skeletal muscle.
AB - Earlier studies have demonstrated that muscle insulin sensitivity to stimulate glucose uptake is enhanced several hours after an acute bout of exercise. Using 5-aminoimidazole-4-carboxamide-ribonucleotide (AICAR), we recently demonstrated that prior activation of AMPK is sufficient to increase insulin sensitivity in mouse skeletal muscle. Here we aimed to determine whether activation of AMPK is also a prerequisite for the ability of muscle contraction to increase insulin sensitivity. We found that prior in situ contraction of m. extensor digitorum longus (EDL) and treadmill exercise increased muscle and whole body insulin sensitivity in wild type (WT) mice, respectively. These effects were not found in AMPKα1α2 muscle-specific knockout mice. Prior in situ contraction did not increase insulin sensitivity in m. soleus from either genotype. Improvement in muscle insulin sensitivity was not associated with enhanced glycogen synthase activity or proximal insulin signaling. However, in WT EDL muscle prior in situ contraction enhanced insulin-stimulated phosphorylation of TBC1D4 Thr(649) and Ser(711) Such findings are also evident in prior exercised and insulin sensitized human skeletal muscle. Collectively, our data suggest that the AMPK-TBC1D4 signaling axis is likely mediating the improved muscle insulin sensitivity after contraction/exercise and illuminates an important and physiological relevant role of AMPK in skeletal muscle.
KW - Faculty of Science
KW - Exercise
KW - Glucose uptake
KW - TBC1D4
KW - AS160
KW - AMP-activated protein kinase
U2 - 10.2337/db16-0530
DO - 10.2337/db16-0530
M3 - Journal article
C2 - 27797909
VL - 66
SP - 598
EP - 612
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 3
ER -
ID: 168290656