The p21-activated kinase 2 (PAK2), but not PAK1, regulates contraction-stimulated skeletal muscle glucose transport
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The p21-activated kinase 2 (PAK2), but not PAK1, regulates contraction-stimulated skeletal muscle glucose transport. / Møller, Lisbeth Liliendal Valbjørn; Nielsen, Ida L; Knudsen, Jonas Roland; Andersen, Nicoline Resen; Jensen, Thomas Elbenhardt; Sylow, Lykke; Richter, Erik A.
In: Physiological Reports, Vol. 8, No. 12, e14460, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The p21-activated kinase 2 (PAK2), but not PAK1, regulates contraction-stimulated skeletal muscle glucose transport
AU - Møller, Lisbeth Liliendal Valbjørn
AU - Nielsen, Ida L
AU - Knudsen, Jonas Roland
AU - Andersen, Nicoline Resen
AU - Jensen, Thomas Elbenhardt
AU - Sylow, Lykke
AU - Richter, Erik A.
N1 - © 2020 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.
PY - 2020
Y1 - 2020
N2 - Aim: Muscle contraction stimulates skeletal muscle glucose transport. Since it occurs independently of insulin, it is an important alternative pathway to increase glucose transport in insulin-resistant states, but the intracellular signaling mechanisms are not fully understood. Muscle contraction activates group I p21-activated kinases (PAKs) in mouse and human skeletal muscle. PAK1 and PAK2 are downstream targets of Rac1, which is a key regulator of contraction-stimulated glucose transport. Thus, PAK1 and PAK2 could be downstream effectors of Rac1 in contraction-stimulated glucose transport. The current study aimed to test the hypothesis that PAK1 and/or PAK2 regulate contraction-induced glucose transport.Methods: Glucose transport was measured in isolated soleus and extensor digitorum longus (EDL) mouse skeletal muscle incubated either in the presence or absence of a pharmacological inhibitor (IPA-3) of group I PAKs or originating from whole-body PAK1 knockout, muscle-specific PAK2 knockout or double whole-body PAK1 and muscle-specific PAK2 knockout mice.Results: IPA-3 attenuated (-22%) the increase in glucose transport in response to electrically stimulated contractions in soleus and EDL muscle. PAK1 was dispensable for contraction-stimulated glucose transport in both soleus and EDL muscle. Lack of PAK2, either alone (-13%) or in combination with PAK1 (-14%), partly reduced contraction-stimulated glucose transport compared to control littermates in EDL, but not soleus muscle.Conclusion: Contraction-stimulated glucose transport in isolated glycolytic mouse EDL muscle is partly dependent on PAK2, but not PAK1.
AB - Aim: Muscle contraction stimulates skeletal muscle glucose transport. Since it occurs independently of insulin, it is an important alternative pathway to increase glucose transport in insulin-resistant states, but the intracellular signaling mechanisms are not fully understood. Muscle contraction activates group I p21-activated kinases (PAKs) in mouse and human skeletal muscle. PAK1 and PAK2 are downstream targets of Rac1, which is a key regulator of contraction-stimulated glucose transport. Thus, PAK1 and PAK2 could be downstream effectors of Rac1 in contraction-stimulated glucose transport. The current study aimed to test the hypothesis that PAK1 and/or PAK2 regulate contraction-induced glucose transport.Methods: Glucose transport was measured in isolated soleus and extensor digitorum longus (EDL) mouse skeletal muscle incubated either in the presence or absence of a pharmacological inhibitor (IPA-3) of group I PAKs or originating from whole-body PAK1 knockout, muscle-specific PAK2 knockout or double whole-body PAK1 and muscle-specific PAK2 knockout mice.Results: IPA-3 attenuated (-22%) the increase in glucose transport in response to electrically stimulated contractions in soleus and EDL muscle. PAK1 was dispensable for contraction-stimulated glucose transport in both soleus and EDL muscle. Lack of PAK2, either alone (-13%) or in combination with PAK1 (-14%), partly reduced contraction-stimulated glucose transport compared to control littermates in EDL, but not soleus muscle.Conclusion: Contraction-stimulated glucose transport in isolated glycolytic mouse EDL muscle is partly dependent on PAK2, but not PAK1.
KW - Faculty of Science
KW - Contraction
KW - Glucose uptake
KW - p21-activated kinase
KW - Skeletal muscle
U2 - 10.14814/phy2.14460
DO - 10.14814/phy2.14460
M3 - Journal article
C2 - 32597567
VL - 8
JO - Physiological Reports
JF - Physiological Reports
SN - 2051-817X
IS - 12
M1 - e14460
ER -
ID: 244042875