Prior AICAR stimulation increases insulin sensitivity in mouse skeletal muscle in an AMPK-dependent manner
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Prior AICAR stimulation increases insulin sensitivity in mouse skeletal muscle in an AMPK-dependent manner. / Kjøbsted, Rasmus; Treebak, Jonas Thue; Fentz, Joachim; Lantier, Louise; Viollet, Benoit; Birk, Jesper Bratz; Schjerling, Peter; Björnholm, Marie; Zierath, Juleen R; Wojtaszewski, Jørgen.
I: Diabetes, Bind 64, Nr. 6, 2015, s. 2042-2055.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Prior AICAR stimulation increases insulin sensitivity in mouse skeletal muscle in an AMPK-dependent manner
AU - Kjøbsted, Rasmus
AU - Treebak, Jonas Thue
AU - Fentz, Joachim
AU - Lantier, Louise
AU - Viollet, Benoit
AU - Birk, Jesper Bratz
AU - Schjerling, Peter
AU - Björnholm, Marie
AU - Zierath, Juleen R
AU - Wojtaszewski, Jørgen
N1 - CURIS 2015 NEXS 199
PY - 2015
Y1 - 2015
N2 - Acute exercise increases glucose uptake in skeletal muscle by an insulin-independent mechanism. In the period after exercise insulin sensitivity to increase glucose uptake is enhanced. The molecular mechanisms underpinning this phenomenon are poorly understood, but appear to involve an increased cell surface abundance of GLUT4. While increased proximal insulin signaling does not seem to mediate this effect, elevated phosphorylation of TBC1D4, a downstream target of both insulin (Akt) and exercise (AMPK) signaling, appears to play a role. The main purpose of this study was to determine whether AMPK activation increases skeletal muscle insulin sensitivity. We found that prior AICAR stimulation of wild-type mouse muscle increases insulin sensitivity to stimulate glucose uptake. However, this was not observed in mice with reduced or ablated AMPK activity in skeletal muscle. Furthermore, prior AICAR stimulation enhanced insulin-stimulated phosphorylation of TBC1D4 at Thr(649) and Ser(711) in wild-type muscle only. These phosphorylation events were positively correlated with glucose uptake. Our results provide evidence to support that AMPK is sufficient to increase skeletal muscle insulin sensitivity. Moreover, TBC1D4 phosphorylation may facilitate the effect of prior AMPK activation to enhance glucose uptake in response to insulin.
AB - Acute exercise increases glucose uptake in skeletal muscle by an insulin-independent mechanism. In the period after exercise insulin sensitivity to increase glucose uptake is enhanced. The molecular mechanisms underpinning this phenomenon are poorly understood, but appear to involve an increased cell surface abundance of GLUT4. While increased proximal insulin signaling does not seem to mediate this effect, elevated phosphorylation of TBC1D4, a downstream target of both insulin (Akt) and exercise (AMPK) signaling, appears to play a role. The main purpose of this study was to determine whether AMPK activation increases skeletal muscle insulin sensitivity. We found that prior AICAR stimulation of wild-type mouse muscle increases insulin sensitivity to stimulate glucose uptake. However, this was not observed in mice with reduced or ablated AMPK activity in skeletal muscle. Furthermore, prior AICAR stimulation enhanced insulin-stimulated phosphorylation of TBC1D4 at Thr(649) and Ser(711) in wild-type muscle only. These phosphorylation events were positively correlated with glucose uptake. Our results provide evidence to support that AMPK is sufficient to increase skeletal muscle insulin sensitivity. Moreover, TBC1D4 phosphorylation may facilitate the effect of prior AMPK activation to enhance glucose uptake in response to insulin.
U2 - 10.2337/db14-1402
DO - 10.2337/db14-1402
M3 - Journal article
C2 - 25552597
VL - 64
SP - 2042
EP - 2055
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 6
ER -
ID: 130291286