ArticleBiochemical pharmacology2014
Signaling of the p21-activated kinase (PAK1) coordinates insulin-stimulated actin remodeling and glucose uptake in skeletal muscle cells.
Article in Biochemical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 65 citations in OpenAlex.
- PAK4 in metabolic diseases: regulation by nutrient signals and therapeutic implications.Experimental & molecular medicine · 2026Review
- TAS1R3 Regulates GTPase Signaling in Human Skeletal Muscle Cells for Glucose Uptake.International journal of molecular sciences · 2025Article
- Inhibition of Unc119b improves insulin sensitivity through potentiation of Rac1 activation in skeletal muscle and brown adipose tissue.Molecular metabolism · 2025Article
- GLUT4 Trafficking and Storage Vesicles: Molecular Architecture, Regulatory Networks, and Their Disruption in Insulin Resistance.International journal of molecular sciences · 2025Review
- p21-Activated Kinase 1 (Pak1) as an Element in Functional and Dysfunctional Interplay Among the Myocardium, Adipose Tissue, and Pancreatic Beta Cells.Comprehensive Physiology · 2025Review
- TAS1R3 influences GTPase-dependent signaling in human islet β-cells.Frontiers in endocrinology · 2025Article
- P21-activated kinase-1 signaling is required to preserve adipose tissue homeostasis and cardiac function.Molecular and cellular biochemistry · 2025Article
- Toward Ameliorating Insulin Resistance: Targeting a Novel PAK1 Signaling Pathway Required for Skeletal Muscle Mitochondrial Function.Antioxidants (Basel, Switzerland) · 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
- Cofilin activation in pancreatic acinar cells plays a pivotal convergent role for mediating CCK-stimulated enzyme secretion and growth.Frontiers in physiology · 2023Article
- Insulin, Muscle Glucose Uptake, and Hexokinase: Revisiting the Road Not Taken.Physiology (Bethesda, Md.) · 2022Review
- 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
- Molecular Mechanism Involved in Carotenoid Metabolism in Post-Smolt Atlantic Salmon: Astaxanthin Metabolism During Flesh Pigmentation and Its Antioxidant Properties.Marine biotechnology (New York, N.Y.) · 2021Article
- Review
- p21-Activated Kinase 1 Is Permissive for the Skeletal Muscle Hypertrophy Induced by Myostatin Inhibition.Frontiers in physiology · 2021Article
- Insulin-stimulated glucose uptake partly relies on p21-activated kinase (PAK)2, but not PAK1, in mouse skeletal muscle.The Journal of physiology · 2020Article
- β-catenin regulates muscle glucose transport via actin remodelling and M-cadherin binding.Molecular metabolism · 2020Article
- Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake.Comprehensive Physiology · 2020Review
- 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
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Skeletal muscle accounts for ∼ 80% of postprandial glucose clearance, and skeletal muscle glucose clearance is crucial for maintaining insulin sensitivity and euglycemia. Insulin-stimulated glucose clearance/uptake entails recruitment of glucose transporter 4 (GLUT4) to the plasma membrane (PM) in a process that requires cortical F-actin remodeling; this process is dysregulated in Type 2 Diabetes. Recent studies have implicated PAK1 as a required element in GLUT4 recruitment in mouse skeletal muscle in vivo, although its underlying mechanism of action and requirement in glucose uptake remains undetermined. Toward this, we have employed the PAK1 inhibitor, IPA3, in studies using L6-GLUT4-myc muscle cells. IPA3 fully ablated insulin-stimulated GLUT4 translocation to the PM, corroborating the observation of ablated insulin-stimulated GLUT4 accumulation in the PM of skeletal muscle from PAK1(-/-) knockout mice. IPA3-treatment also abolished insulin-stimulated glucose uptake into skeletal myotubes. Mechanistically, live-cell imaging of myoblasts expressing the F-actin biosensor LifeAct-GFP treated with IPA3 showed blunting of the normal insulin-induced cortical actin remodeling. This blunting was underpinned by a loss of normal insulin-stimulated cofilin dephosphorylation in IPA3-treated myoblasts. These findings expand upon the existing model of actin remodeling in glucose uptake, by placing insulin-stimulated PAK1 signaling as a required upstream step to facilitate actin remodeling and subsequent cofilin dephosphorylation. Active, dephosphorylated cofilin then provides the G-actin substrate for continued F-actin remodeling to facilitate GLUT4 vesicle translocation for glucose uptake into the skeletal muscle cell.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.