ArticleThe Journal of physiology2020
Insulin-stimulated glucose uptake partly relies on p21-activated kinase (PAK)2, but not PAK1, in mouse skeletal muscle.
Article in The Journal of physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 23 citations in OpenAlex.
- Relaxin-2: Shaping the Proteomic Landscape of Skeletal Muscle Physiology, Glucose Trafficking, and Mitochondrial Function in Rat.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The insulin signalling network.Nature metabolism · 2025Review
- Nitric oxide in modulating oxidative stress mediated skeletal muscle insulin resistance.Molecular biology reports · 2024Review
- Gastrodin ameliorates cognitive dysfunction in diabetes by inhibiting PAK2 phosphorylation.Aging · 2023Article
- The Rho guanine dissociation inhibitor α inhibits skeletal muscle Rac1 activity and insulin action.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Hormonal regulation of metabolism-recent lessons learned from insulin and estrogen.Clinical science (London, England : 1979) · 2023Review
- Gene deletion of γ-actin impairs insulin-stimulated skeletal muscle glucose uptake in growing mice but not in mature adult mice.Physiological reports · 2022Article
- Changes in Skeletal Muscle PAK1 Levels Regulate Tissue Crosstalk to Impact Whole Body Glucose Homeostasis.Frontiers in endocrinology · 2022Article
- Exocytosis Proteins: Typical and Atypical Mechanisms of Action in Skeletal Muscle.Frontiers in endocrinology · 2022Review
- Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.Journal of medicinal chemistry · 2021Review
- Review
- p21-Activated Kinase 1 Is Permissive for the Skeletal Muscle Hypertrophy Induced by Myostatin Inhibition.Frontiers in physiology · 2021Article
- The Role of p21-Activated Kinases in Cancer and Beyond: Where Are We Heading?Frontiers in cell and developmental biology · 2021Review
- β-catenin regulates muscle glucose transport via actin remodelling and M-cadherin binding.Molecular metabolism · 2020Article
- The p21-activated kinase 2 (PAK2), but not PAK1, regulates contraction-stimulated skeletal muscle glucose transport.Physiological reports · 2020Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 3 countries.
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Abstract
key pointsMuscle-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. ABSTRACT: 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.
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