ArticleDiabetes2012
The novel therapeutic effect of phosphoinositide 3-kinase-γ inhibitor AS605240 in autoimmune diabetes.
Article in Diabetes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 39 citations in OpenAlex.
- Ras suppression potentiates rear actomyosin contractility-driven cell polarization and migration.Nature cell biology · 2024Article
- Nanotargeted Delivery of Immune Therapeutics in Type 1 Diabetes.Advanced materials (Deerfield Beach, Fla.) · 2023Article
- Actuation of single downstream nodes in growth factor network steers immune cell migration.Developmental cell · 2023Article
- AS-605240 Blunts Osteoporosis by Inhibition of Bone Resorption.Drug design, development and therapy · 2023Article
- Control of CD4Current topics in microbiology and immunology · 2022Article
- Syngeneic bone marrow transplantation in combination with PI3K inhibitor reversed hyperglycemia in later-stage streptozotocin-induced diabetes.Annals of translational medicine · 2021Article
- A systems-level study reveals host-targeted repurposable drugs against SARS-CoV-2 infection.Molecular systems biology · 2021Article
- Phosphoinositide 3-kinase inhibitor AS605240 ameliorates streptozotocin-induced Alzheimer's disease like sporadic dementia in experimental rats.EXCLI journal · 2020Article
- PI3-Kinase δγ Catalytic Isoforms Regulate the Th-17 Response in Tuberculosis.Frontiers in immunology · 2019Review
- PI3Kγ (Phosphoinositide 3-Kinase-γ) Inhibition Attenuates Tissue-Type Plasminogen Activator-Induced Brain Hemorrhage and Improves Microvascular Patency After Embolic Stroke.Hypertension (Dallas, Tex. : 1979) · 2019Article
- Flavonoids inhibit cell proliferation and induce apoptosis and autophagy through downregulation of PI3Kγ mediated PI3K/AKT/mTOR/p70S6K/ULK signaling pathway in human breast cancer cells.Scientific reports · 2018Article
- Blocking IFNAR1 inhibits multiple myeloma-driven Treg expansion and immunosuppression.The Journal of clinical investigation · 2018Article
- Regulation of T cell alloimmunity by PI3Kγ and PI3Kδ.Nature communications · 2017Article
- Metabolically active CD4+ T cells expressing Glut1 and OX40 preferentially harbor HIV during in vitro infection.FEBS letters · 2017Article
- PI3Kγ Deficient NOD-Mice Are Protected from Diabetes by Restoring the Balance of Regulatory to Effector-T-Cells.PloS one · 2017Article
- Phosphatidylinositol 3-Kinase γ is required for the development of experimental cerebral malaria.PloS one · 2015Article
- Advances in the cellular immunological pathogenesis of type 1 diabetes.Journal of cellular and molecular medicine · 2014Review
- Selective inhibitors of phosphoinositide 3-kinase delta: modulators of B-cell function with potential for treating autoimmune inflammatory diseases and B-cell malignancies.Frontiers in immunology · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 1 diabetes (T1D) remains a major health problem worldwide, with a steadily rising incidence yet no cure. Phosphoinositide 3-kinase-γ (PI3Kγ), a member of a family of lipid kinases expressed primarily in leukocytes, has been the subject of substantial research for its role in inflammatory diseases. However, the role of PI3Kγ inhibition in suppressing autoimmune T1D remains to be explored. We tested the role of the PI3Kγ inhibitor AS605240 in preventing and reversing diabetes in NOD mice and assessed the mechanisms by which this inhibition abrogates T1D. Our data indicate that the PI3Kγ pathway is highly activated in T1D. In NOD mice, we found upregulated expression of phosphorylated Akt (PAkt) in splenocytes. Notably, T regulatory cells (Tregs) showed significantly lower expression of PAkt compared with effector T cells. Inhibition of the PI3Kγ pathway by AS605240 efficiently suppressed effector T cells and induced Treg expansion through the cAMP response element-binding pathway. AS605240 effectively prevented and reversed autoimmune diabetes in NOD mice and suppressed T-cell activation and the production of inflammatory cytokines by autoreactive T cells in vitro and in vivo. These studies demonstrate the key role of the PI3Kγ pathway in determining the balance of Tregs and autoreactive cells regulating autoimmune diabetes.
Indexed as
Identifiers
What OpenQuestion holds
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.