ArticleDiabetes2012
NADPH oxidase NOX2 defines a new antagonistic role for reactive oxygen species and cAMP/PKA in the regulation of insulin secretion.
Article in Diabetes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 121 citations in OpenAlex.
- The paracrine signalling between endothelial and pancreatic β-cells: implications for oxidative stress and diabetes.Journal of endocrinological investigation · 2026Review
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- Expression, localization and regulation of NADPH oxidases in pancreatic beta cells.Redox report : communications in free radical research · 2025Article
- A TRPM2-Driven Signalling Cycle Orchestrates Abnormal Inter-Organelle Crosstalk in Cardiovascular and Metabolic Diseases.Biomolecules · 2025Review
- Inter-Organelle Crosstalk in Oxidative Distress: A Unified TRPM2-NOX2 Mediated Vicious Cycle Involving CaAntioxidants (Basel, Switzerland) · 2025Review
- Ex vivo lung perfusion with GLP-1R agonist mitigates ischemia/reperfusion injury through pyroptosis modulation in lung transplantation- an experimental study.International journal of surgery (London, England) · 2025Article
- Unraveling the Mystery of Insulin Resistance: From Principle Mechanistic Insights and Consequences to Therapeutic Interventions.International journal of molecular sciences · 2025Review
- NADPH oxidase 5 is a novel susceptibility gene for type 2 diabetes mellitus.Archives of endocrinology and metabolism · 2024Article
- NADPH Dynamics: Linking Insulin Resistance and β-Cells Ferroptosis in Diabetes Mellitus.International journal of molecular sciences · 2023Review
- Redox Balance in Type 2 Diabetes: Therapeutic Potential and the Challenge of Antioxidant-Based Therapy.Antioxidants (Basel, Switzerland) · 2023Review
- Anti-oxidant effect of nitrite in the pancreatic islets of type 2 diabetic male rats.Iranian journal of basic medical sciences · 2023Article
- The old second messenger cAMP teams up with novel cell death mechanisms: potential translational therapeutical benefit for Alzheimer's disease and Parkinson's disease.Frontiers in physiology · 2023Review
- Role of Reactive Oxygen Species in Glucose Metabolism Disorder in Diabetic Pancreatic β-Cells.Biomolecules · 2022Review
- The loss of pancreatic islet NADPH oxidase (NOX)2 improves islet transplantation.Redox biology · 2022Article
- Metabolic Adaptions/Reprogramming in Islet Beta-Cells in Response to Physiological Stimulators-What Are the Consequences.Antioxidants (Basel, Switzerland) · 2022Review
- Lipotoxicity and β-Cell Failure in Type 2 Diabetes: Oxidative Stress Linked to NADPH Oxidase and ER Stress.Cells · 2021Review
- Butyrate Protects Pancreatic Beta Cells from Cytokine-Induced Dysfunction.International journal of molecular sciences · 2021Article
- Early Cytokine-Induced Transient NOX2 Activity Is ER Stress-Dependent and Impacts β-Cell Function and Survival.Antioxidants (Basel, Switzerland) · 2021Article
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In insulin-secreting cells, expression of NADPH oxidase (NOX), a potent source of ROS, has been reported, along with controversial findings regarding its function. Here, the role of NOXs was investigated: first by expression and cellular localization in mouse and human pancreatic islets, and then by functional studies in islets isolated from Nox isoform-specific knockout mice. Both human and mouse β-cells express NOX, in particular NOX2. With use of Nox isoform-specific knockout mice, functional analysis revealed Nox2 as the predominant isoform. In human islets, NOX2 colocalized with both insulin granules and endosome/lysosome membranes. Nox2-deficient islets stimulated with 22.8 mmol/L glucose exhibited potentiation of insulin release compared with controls, an effect confirmed with in vitro knockdown of Nox2. The enhanced secretory function in Nox2-deficient islets was associated with both lower superoxide levels and elevated cAMP concentrations. In control islets, GLP-1 and other cAMP inducers suppressed glucose-induced ROS production similarly to Nox2 deficiency. Inhibiting cAMP-dependent protein kinase reduced the secretory response in Nox2-null islets, although not in control islets. This study ascribes a new role for NOX2 in pancreatic β-cells as negative modulator of the secretory response, reducing cAMP/PKA signaling secondary to ROS generation. Results also show reciprocal inhibition between the cAMP/PKA pathway and ROS.
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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.