Insulin-stimulated glucose uptake partly relies on p21-activated kinase (PAK)2, but not PAK1, in mouse skeletal muscle.
GLUT4 translocation
glucose uptake
insulin
metabolism
p21-activated kinases
skeletal muscle
Journal
The Journal of physiology
ISSN: 1469-7793
Titre abrégé: J Physiol
Pays: England
ID NLM: 0266262
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
08
06
2020
accepted:
24
08
2020
pubmed:
28
8
2020
medline:
2
3
2021
entrez:
27
8
2020
Statut:
ppublish
Résumé
Muscle-specific genetic ablation of p21-activated kinase (PAK)2, but not whole-body PAK1 knockout, impairs glucose tolerance in mice. Insulin-stimulated glucose uptake partly relies on PAK2 in glycolytic extensor digitorum longus muscle By contrast to previous reports, PAK1 is dispensable for insulin-stimulated glucose uptake in mouse muscle. 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.
Identifiants
pubmed: 32844438
doi: 10.1113/JP280294
pmc: PMC7771197
mid: NIHMS1649808
doi:
Substances chimiques
Insulin
0
p21-Activated Kinases
EC 2.7.11.1
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5351-5377Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR046207
Pays : United States
Organisme : The Danish Council for Independent Research, Medical Sciences
ID : 6108-00203
Organisme : NIAMS NIH HHS
ID : R01 AR070231
Pays : United States
Organisme : NIAMS NIH HHS
ID : AR070231
Pays : United States
Organisme : NIAMS NIH HHS
ID : AR046207
Pays : United States
Organisme : The Danish Council for Independent Research, Medical Sciences
ID : DFF-4004-00233
Organisme : Danish Diabetes Academy (funded by The Novo Nordisk Foundation)
ID : NNF17SA0031406
Informations de copyright
© 2020 The Authors. The Journal of Physiology © 2020 The Physiological Society.
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