ArticleInternational journal of biological sciences2022
Ebselen enhances insulin sensitivity and decreases oxidative stress by inhibiting SHIP2 and protects from inflammation in diabetic mice.
Article in International journal of biological sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Ebselen attenuates selected cardiac and vascular alterations in rats exposed to a cholesterol/cholic acid diet.Journal of molecular histology · 2026Article
- Ebselen restores mitochondrial function through metabolic rewiring in Barth syndrome and related mitochondrial diseases.EMBO molecular medicine · 2026Article
- Small Molecule Insulin Sensitisers: New Leads and Targets for Next-Generation Insulin Sensitising Strategies.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- The power of five - inositol polyphosphate 5-phosphatase gene mutations at the intersection of development and disease.FEBS letters · 2026Review
- Unraveling the Physicochemical Landscape of Organoselenium Compounds in Nanocarrier Systems.Chemical record (New York, N.Y.) · 2026Review
- Paeoniflorin protects against NAFLD through antioxidant, anti-inflammatory effects and restoration of gut microbiota homeostasis.Frontiers in microbiology · 2026Article
- Advances in biomedical applications of Se-based nanozymes.Journal of nanobiotechnology · 2025Review
- Review
- NCAM1-SHIP2 axis upon recognizing microbes inhibits the expressions of inflammatory factors through P38-H3K4me and P38-NF-κB pathways in oyster.Cell communication and signaling : CCS · 2025Article
- TangNaikang Formula Alleviates Podocyte Injury in Diabetic Nephropathy by Modulating the SHIP2/PI3K/AKT Pathway.Journal of diabetes research · 2025Article
- Metformin Effects on SHIP2, AMPKs and Gut Microbiota: Recent Updates on Pharmacology.Current medicinal chemistry · 2025Review
- Unveiling the Role of Oxidative Stress in Cochlear Hair Cell Death: Prospective Phytochemical Therapeutics against Sensorineural Hearing Loss.International journal of molecular sciences · 2024Review
- Role of oxidative stress in impaired type II diabetic bone repair: scope for antioxidant therapy intervention?Frontiers in dental medicine · 2024Review
- Redox Balance in Type 2 Diabetes: Therapeutic Potential and the Challenge of Antioxidant-Based Therapy.Antioxidants (Basel, Switzerland) · 2023Review
- The emerging roles of PHOSPHO1 and its regulated phospholipid homeostasis in metabolic disorders.Frontiers in physiology · 2022Review
- The non-linear relationship between triglyceride-glucose index and risk of chronic kidney disease in hypertensive patients with abnormal glucose metabolism: A cohort study.Frontiers in medicine · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ebselen, a multifunctional organoselenium compound, has been recognized as a potential treatment for diabetes-related disorders. However, the underlying mechanisms whereby ebselen regulates metabolic pathways remain elusive. We discovered that ebselen inhibits lipid phosphatase SHIP2 (Src homology 2 domain-containing inositol-5-phosphatase 2), an emerging drug target to ameliorate insulin resistance in diabetes. We found that ebselen directly binds to and inhibits the catalytic activity of the recombinant SHIP2 phosphatase domain and SHIP2 in cultured cells, the skeletal muscle and liver of the diabetic db/db mice, and the liver of the SHIP2 overexpressing (SHIP2-Tg) mice. Ebselen increased insulin-induced Akt phosphorylation in cultured myotubes, enhanced insulin sensitivity and protected liver tissue from lipid peroxidation and inflammation in the db/db mice, and improved glucose tolerance more efficiently than metformin in the SHIP2-Tg mice. SHIP2 overexpression abrogated the ability of ebselen to induce glucose uptake and reduce ROS production in myotubes and blunted the effect of ebselen to inhibit SHIP2 in the skeletal muscle of the SHIP2-Tg mice. Our data reveal ebselen as a potent SHIP2 inhibitor and demonstrate that the ability of ebselen to ameliorate insulin resistance and act as an antioxidant is at least in part mediated by the reduction of SHIP2 activity.
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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.