Insulin-stimulated glucose uptake partly relies on p21-activated kinase (PAK)2, but not PAK1, in mouse skeletal muscle
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Insulin-stimulated glucose uptake partly relies on p21-activated kinase (PAK)2, but not PAK1, in mouse skeletal muscle. / Møller, Lisbeth Liliendal Valbjørn; Jaurji, Merna; Kjøbsted, Rasmus; Joseph, Giselle A; Madsen, Agnete B; Knudsen, Jonas Roland; Lundsgaard, Annemarie; Andersen, Nicoline Resen; Schjerling, Peter; Jensen, Thomas Elbenhardt; Krauss, Robert S; Richter, Erik A.; Sylow, Lykke.
In: Journal of Physiology, Vol. 598, No. 23, 2020, p. 5351-5377.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Insulin-stimulated glucose uptake partly relies on p21-activated kinase (PAK)2, but not PAK1, in mouse skeletal muscle
AU - Møller, Lisbeth Liliendal Valbjørn
AU - Jaurji, Merna
AU - Kjøbsted, Rasmus
AU - Joseph, Giselle A
AU - Madsen, Agnete B
AU - Knudsen, Jonas Roland
AU - Lundsgaard, Annemarie
AU - Andersen, Nicoline Resen
AU - Schjerling, Peter
AU - Jensen, Thomas Elbenhardt
AU - Krauss, Robert S
AU - Richter, Erik A.
AU - Sylow, Lykke
N1 - This article is protected by copyright. All rights reserved.
PY - 2020
Y1 - 2020
N2 - The group I p21‐activated kinase (PAK) isoforms PAK1 and PAK2 are activated in response to insulin in skeletal muscle and PAK1/2 signalling is impaired in insulin‐resistant mouse and human skeletal muscle. Interestingly, PAK1 has been suggested to be required for insulin‐stimulated glucose transporter 4 translocation in mouse skeletal muscle. Therefore, the present study aimed to examine the role of PAK1 in insulin‐stimulated muscle glucose uptake. The pharmacological inhibitor of group I PAKs, IPA‐3 partially reduced (–20%) insulin‐stimulated glucose uptake in isolated mouse soleus muscle (P < 0.001). However, because there was no phenotype with genetic ablation of PAK1 alone, consequently, the relative requirement for PAK1 and PAK2 in whole‐body glucose homeostasis and insulin‐stimulated muscle glucose uptake was investigated. Whole‐body respiratory exchange ratio was largely unaffected in whole‐body PAK1 knockout (KO), muscle‐specific PAK2 KO and in mice with combined whole‐body PAK1 KO and muscle‐specific PAK2 KO. By contrast, glucose tolerance was mildly impaired in mice lacking PAK2 specifically in muscle, but not PAK1 KO mice. Moreover, while PAK1 KO muscles displayed normal insulin‐stimulated glucose uptake in vivo and in isolated muscle, insulin‐stimulated glucose uptake was slightly reduced in isolated glycolytic extensor digitorum longus muscle lacking PAK2 alone (–18%) or in combination with PAK1 KO (–12%) (P < 0.05). In conclusion, glucose tolerance and insulin‐stimulated glucose uptake partly rely on PAK2 in glycolytic mouse muscle, whereas PAK1 is dispensable for whole‐body glucose homeostasis and insulin‐stimulated muscle glucose uptake.
AB - The group I p21‐activated kinase (PAK) isoforms PAK1 and PAK2 are activated in response to insulin in skeletal muscle and PAK1/2 signalling is impaired in insulin‐resistant mouse and human skeletal muscle. Interestingly, PAK1 has been suggested to be required for insulin‐stimulated glucose transporter 4 translocation in mouse skeletal muscle. Therefore, the present study aimed to examine the role of PAK1 in insulin‐stimulated muscle glucose uptake. The pharmacological inhibitor of group I PAKs, IPA‐3 partially reduced (–20%) insulin‐stimulated glucose uptake in isolated mouse soleus muscle (P < 0.001). However, because there was no phenotype with genetic ablation of PAK1 alone, consequently, the relative requirement for PAK1 and PAK2 in whole‐body glucose homeostasis and insulin‐stimulated muscle glucose uptake was investigated. Whole‐body respiratory exchange ratio was largely unaffected in whole‐body PAK1 knockout (KO), muscle‐specific PAK2 KO and in mice with combined whole‐body PAK1 KO and muscle‐specific PAK2 KO. By contrast, glucose tolerance was mildly impaired in mice lacking PAK2 specifically in muscle, but not PAK1 KO mice. Moreover, while PAK1 KO muscles displayed normal insulin‐stimulated glucose uptake in vivo and in isolated muscle, insulin‐stimulated glucose uptake was slightly reduced in isolated glycolytic extensor digitorum longus muscle lacking PAK2 alone (–18%) or in combination with PAK1 KO (–12%) (P < 0.05). In conclusion, glucose tolerance and insulin‐stimulated glucose uptake partly rely on PAK2 in glycolytic mouse muscle, whereas PAK1 is dispensable for whole‐body glucose homeostasis and insulin‐stimulated muscle glucose uptake.
KW - Faculty of Science
KW - Skeletal muscle
KW - Insulin
KW - Glucose uptake
KW - GLUT4 translocation
KW - p21-activated kinases
KW - Metabolism
U2 - 10.1113/JP280294
DO - 10.1113/JP280294
M3 - Journal article
C2 - 32844438
VL - 598
SP - 5351
EP - 5377
JO - The Journal of Physiology
JF - The Journal of Physiology
SN - 0022-3751
IS - 23
ER -
ID: 247876643