ArticleMetabolism: clinical and experimental2021
A requirement for PAK1 to support mitochondrial function and maintain cellular redox balance via electron transport chain proteins to prevent β-cell apoptosis.
Article in Metabolism: clinical and experimental, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- HM568 Enhances NADMolecular neurobiology · 2026Article
- Multitrait GWAS and functional validation reveal genetic loci for gastric cancer.Nature communications · 2026Article
- The Role of the p21-Activated Kinase Family in Tumor Immunity.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
- DOC2b enrichment mitigates proinflammatory cytokine-induced CXCL10 expression by attenuating IKKβ and STAT-1 signaling in human islets.Metabolism: clinical and experimental · 2025Article
- 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
- Discovery of a Novel Selective PAK1/HDAC6/HDAC10 Inhibitor ZMF-25 that Induces Mitochondrial Metabolic Breakdown and Autophagy-Related Cell Death in Triple-Negative Breast Cancer.Research (Washington, D.C.) · 2025Article
- Regulation of Vascular Injury and Repair by P21-Activated Kinase 1 and P21-Activated Kinase 2: Therapeutic Potential and Challenges.Biomolecules · 2024Review
- Article
- Mitochondrial Dysfunction, Oxidative Stress, and Inter-Organ Miscommunications in T2D Progression.International journal of molecular sciences · 2024Review
- Mechanism study of oleanolic acid derivative, K73-03, inducing cell apoptosis in hepatocellular carcinoma.Cancer cell international · 2024Article
- Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes.Frontiers in molecular biosciences · 2024Review
- CD44 Intracellular Domain: A Long Tale of a Short Tail.Cancers · 2023Review
- Toward Ameliorating Insulin Resistance: Targeting a Novel PAK1 Signaling Pathway Required for Skeletal Muscle Mitochondrial Function.Antioxidants (Basel, Switzerland) · 2023Article
- The P21-Activated Kinase 1 and 2 As Potential Therapeutic Targets for the Management of Cardiovascular Disease.International journal of drug discovery and pharmacology · 2022Article
- p21-activated kinase 1 (PAK1) as a therapeutic target for cardiotoxicity.Archives of toxicology · 2022Review
- Mitophagy: An Emerging Target in Ocular Pathology.Investigative ophthalmology & visual science · 2021Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
objectivep21 (Cdc42/Rac1) activated Kinase 1 (PAK1) is a candidate susceptibility factor for type 2 diabetes (T2D). PAK1 is depleted in the islets from T2D donors, compared to control individuals. In addition, whole-body PAK1 knock out (PAK1-KO) in mice worsens the T2D-like effects of high-fat diet. The current study tested the effects of modulating PAK1 levels only in β-cells. MATERIALS/
methodsβ-cell-specific inducible PAK1 KO (βPAK1-iKO) mice were generated and used with human β-cells and T2D islets to evaluate β-cell function.
resultsβPAK1-iKO mice exhibited glucose intolerance and elevated β-cell apoptosis, but without peripheral insulin resistance. β-cells from βPAK-iKO mice also contained fewer mitochondria per cell. At the cellular level, human PAK1-deficient β-cells showed blunted glucose-stimulated insulin secretion and reduced mitochondrial function. Mitochondria from human PAK1-deficient β-cells were deficient in the electron transport chain (ETC) subunits CI, CIII, and CIV; NDUFA12, a CI complex protein, was identified as a novel PAK1 binding partner, and was significantly reduced with PAK1 knockdown. PAK1 knockdown disrupted the NAD
conclusionsThese findings support a protective function for PAK1 in β-cells. The results support a new model whereby the PAK1 in the β-cell plays a required role upstream of mitochondrial function, via maintaining ETC protein levels and averting stress-induced β-cell apoptosis to retain healthy functional β-cell mass.
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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.