ArticleThe Journal of biological chemistry2011
Inhibition or ablation of p21-activated kinase (PAK1) disrupts glucose homeostatic mechanisms in vivo.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 134 citations in OpenAlex.
- Trial
- PAK4 in metabolic diseases: regulation by nutrient signals and therapeutic implications.Experimental & molecular medicine · 2026Review
- Targeting Cdc42: Novel Approaches in Cardiovascular Disorders.Current protein & peptide science · 2026Review
- 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
- Review
- Beta cell-specific PAK1 enrichment ameliorates diet-induced glucose intolerance in mice by promoting insulin biogenesis and minimising beta cell apoptosis.Diabetologia · 2025Article
- P21-activated kinase-1 signaling is required to preserve adipose tissue homeostasis and cardiac function.Molecular and cellular biochemistry · 2025Article
- Article
- PAK4 phosphorylates and inhibits AMPKα to control glucose uptake.Nature communications · 2024Article
- Mitochondrial Dysfunction, Oxidative Stress, and Inter-Organ Miscommunications in T2D Progression.International journal of molecular sciences · 2024Review
- Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes.Frontiers in molecular biosciences · 2024Review
- The Role of Cdc42 in the Insulin and Leptin Pathways Contributing to the Development of Age-Related Obesity.Nutrients · 2023Review
- Toward Ameliorating Insulin Resistance: Targeting a Novel PAK1 Signaling Pathway Required for Skeletal Muscle Mitochondrial Function.Antioxidants (Basel, Switzerland) · 2023Article
- Probing the diabetes and colorectal cancer relationship using gene - environment interaction analyses.British journal of cancer · 2023Article
- Article
- Time-restricted eating alters the 24-hour profile of adipose tissue transcriptome in men with obesity.Obesity (Silver Spring, Md.) · 2023Article
- Novel roles of mTORC2 in regulation of insulin secretion by actin filament remodeling.American journal of physiology. Endocrinology and metabolism · 2022Article
- Mechanisms by Which Skeletal Muscle Myokines Ameliorate Insulin Resistance.International journal of molecular sciences · 2022Review
- GWAS in people of Middle Eastern descent reveals a locus protective of kidney function-a cross-sectional study.BMC medicine · 2022Article
- Dysregulation of β-Cell Proliferation in Diabetes: Possibilities of Combination Therapy in the Development of a Comprehensive Treatment.Biomedicines · 2022Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The p21-activated kinase PAK1 is implicated in tumorigenesis, and efforts to inhibit PAK1 signaling as a means to induce tumor cell apoptosis are underway. However, PAK1 has also been implicated as a positive effector of mechanisms in clonal pancreatic beta cells and skeletal myotubes that would be crucial to maintaining glucose homeostasis in vivo. Of relevance, human islets of Type 2 diabetic donors contained ~80% less PAK1 protein compared with non-diabetics, implicating PAK1 in islet signaling/scaffolding functions. Mimicking this, islets from PAK1(-/-) knock-out mice exhibited profound defects in the second/sustained-phase of insulin secretion. Reiteration of this specific defect by human islets treated with the PAK1 signaling inhibitor IPA3 revealed PAK1 signaling to be of primary functional importance. Analyses of human and mouse islet beta cell signaling revealed PAK1 activation to be 1) dependent upon Cdc42 abundance, 2) crucial for signaling downstream to activate ERK1/2, but 3) dispensable for cofilin phosphorylation. Importantly, the PAK1(-/-) knock-out mice were found to exhibit whole body glucose intolerance in vivo. Exacerbating this, the PAK1(-/-) knock-out mice also exhibited peripheral insulin resistance. Insulin resistance was coupled to ablation of insulin-stimulated GLUT4 translocation in skeletal muscle from PAK1(-/-) knock-out mice, and in sharp contrast to islet beta cells, skeletal muscle PAK1 loss was underscored by defective cofilin phosphorylation but normal ERK1/2 activation. Taken together, these data provide the first human islet and mammalian in vivo data unveiling the key and crucial roles for differential PAK1 signaling in the multi-tissue regulation of whole body glucose homeostasis.
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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 OpenQuestion graph.