ArticleMolecular biology of the cell2005
The major target of the endogenously generated reactive oxygen species in response to insulin stimulation is phosphatase and tensin homolog and not phosphoinositide-3 kinase (PI-3 kinase) in the PI-3 kinase/Akt pathway.
Article in Molecular biology of the cell, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 171 citations in OpenAlex.
- The effect of exercise-intensity on skeletal muscle stress kinase and insulin protein signaling.PloS one · 2017Trial
- 1,1-Diethoxyethane increases insulin sensitivity and ameliorates obesity and dyslipidemia in mice fed high-fat diet.npj metabolic health and disease · 2026Article
- Redox Homeostasis in Metabolic Syndrome and Type II Diabetes: Role of Skeletal Muscle and Impact of Gold-Standard Treatments.International journal of molecular sciences · 2025Review
- Redox Regulation of PTEN by Reactive Oxygen Species: Its Role in Physiological Processes.Antioxidants (Basel, Switzerland) · 2024Review
- The Role of Oxidative Inactivation of Phosphatase PTEN and TCPTP in Fatty Liver Disease.Antioxidants (Basel, Switzerland) · 2023Review
- Acute exercise and high-glucose ingestion elicit dynamic and individualized responses in systemic markers of redox homeostasis.Frontiers in immunology · 2023Article
- Potential Roles of Glucagon-Like Peptide-1 and Its Analogues in Dementia Targeting Impaired Insulin Secretion and Neurodegeneration.Degenerative neurological and neuromuscular disease · 2022Review
- Reactive oxygen species in exercise and insulin resistance: Working towards personalized antioxidant treatment.Redox biology · 2021Review
- Pleiotropic and Potentially Beneficial Effects of Reactive Oxygen Species on the Intracellular Signaling Pathways in Endothelial Cells.Antioxidants (Basel, Switzerland) · 2021Review
- Redox regulation of the insulin signalling pathway.Redox biology · 2021Review
- Article
- FOXO activity adaptation safeguards the hematopoietic stem cell compartment in hyperglycemia.Blood advances · 2020Article
- Modulation of PTEN by hexarelin attenuates coronary artery ligation-induced heart failure in ratsTurkish journal of medical sciences · 2019Article
- Association of PTEN expression with liver function and inflammatory changes in patients with liver cancer after chemotherapy.Oncology letters · 2018Article
- Bidirectional modulation of insulin action by reactive oxygen species in 3T3‑L1 adipocytes.Molecular medicine reports · 2018Article
- Oxidative stress and cellular pathologies in Parkinson's disease.Molecular brain · 2017Review
- Decreased phosphatase PTEN amplifies PI3K signaling and enhances proinflammatory cytokine release in COPD.American journal of physiology. Lung cellular and molecular physiology · 2017Article
- Redox Regulation of the Tumor Suppressor PTEN by Hydrogen Peroxide and Tert-Butyl Hydroperoxide.International journal of molecular sciences · 2017Article
- Exercise and Glycemic Control: Focus on Redox Homeostasis and Redox-Sensitive Protein Signaling.Frontiers in endocrinology · 2017Review
- Hepatocyte glutathione peroxidase-1 deficiency improves hepatic glucose metabolism and decreases steatohepatitis in mice.Diabetologia · 2016Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphoinositide-3 kinase (PI-3 kinase) and its downstream signaling molecules PDK-1 and Akt were analyzed in SK-N-SH and SK-N-BE(2) human neuroblastoma cell lines. When cells were stimulated with insulin, PI-3 kinase was activated in both cell lines, whereas the translocation of PDK-1 to the membrane fraction and phosphorylated Akt were observed only in SK-N-SH cells. Analyses of the insulin-mediated reactive oxygen species (ROS) generation and Phosphatase and Tensin homolog (PTEN) oxidation indicate that PTEN oxidation occurred in SK-N-SH cells, which can produce ROS, but not in SK-N-BE(2) cells, which cannot increase ROS in response to insulin stimulation. When SK-N-SH cells were pretreated with the NADPH oxidase inhibitor diphenyleneiodonium chloride before insulin stimulation, insulin-mediated translocation of PDK-1 to the membrane fraction and phosphorylation of Akt were remarkably reduced, whereas PI-3 kinase activity was not changed significantly. These results indicate that not only PI-3 kinase activation but also inhibition of PTEN by ROS is needed to increase cellular level of phosphatidylinositol 3,4,5-trisphosphate for recruiting downstream signaling molecules such as PDK-1 and Akt in insulin-mediated signaling. Moreover, the ROS generated by insulin stimulation mainly contributes to the inactivation of PTEN and not to the activation of PI-3 kinase in the PI-3 kinase/Akt pathway.
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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.