ArticleThe Journal of biological chemistry2010
Regulation of insulin receptor substrate 1 (IRS-1)/AKT kinase-mediated insulin signaling by O-Linked beta-N-acetylglucosamine in 3T3-L1 adipocytes.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 2 of them syntheses that pooled it.
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
105 citing papers in PubMed, 2 syntheses or guidelines pooled it, 173 citations in OpenAlex.
- Tools for investigating O-GlcNAc in signaling and other fundamental biological pathways.The Journal of biological chemistry · 2024Pooled it
- Insulin gene mutations and posttranslational and translocation defects: associations with diabetes.Endocrine · 2020Pooled it
- Seeking the Mechanism for Reversal of Enhanced Insulin Sensitivity After Acute Exercise.Exercise and sport sciences reviews · 2026Review
- O-GlcNAcylation as a Metabolic Integrator in Cardiovascular Physiology and Disease.International journal of molecular sciences · 2026Review
- Cell cycle regulation in cancer cells by O-GlcNAcylation.Glycoconjugate journal · 2025Review
- Emerging Roles of Post-Translational Modifications in Metabolic Homeostasis and Type 2 Diabetes.International journal of molecular sciences · 2025Review
- Protein O-GlcNAcylation in reproductive biology and the impact of metabolic disease.Human reproduction update · 2025Review
- Resveratrol Impairs Insulin Signaling in Hepatic Cells via Activation of PKC and PTP1B Pathways.International journal of molecular sciences · 2025Article
- O-GlcNAcylation in Endocrinology: The Sweet Link.Endocrinology · 2025Review
- Association between O-GlcNAc levels and platelet function in obese insulin-resistant subjects.Glycoconjugate journal · 2024Article
- The post-translational modification O-GlcNAc is a sensor and regulator of metabolism.Open biology · 2024Review
- Post-translational modifications of pyruvate dehydrogenase complex in cardiovascular disease.iScience · 2024Review
- Neddylation of insulin receptor substrate acts as a bona fide regulator of insulin signaling and its implications for cancer cell migration.Cancer gene therapy · 2024Article
- Post-Translational Modifications and Diabetes.Biomolecules · 2024Review
- Phosphorylation Codes in IRS-1 and IRS-2 Are Associated with the Activation/Inhibition of Insulin Canonical Signaling Pathways.Current issues in molecular biology · 2024Review
- O-GlcNAcylation in ischemic diseases.Frontiers in pharmacology · 2024Review
- Diabetes Pharmacotherapy and its effects on the Skeletal Muscle Energy Metabolism.Mini reviews in medicinal chemistry · 2024Review
- Monoamine oxidase mediated oxidative stress: a potential molecular and biochemical crux in the pathogenesis of obesity.Molecular biology reports · 2023Review
- Deciphering the Properties and Functions of Glycoproteins Using Quantitative Proteomics.Journal of proteome research · 2023Review
- Increased hepatic Akt phosphorylation alleviated glucose intolerance and improved liver function in leptin-deficient mice.Clinical and experimental hepatology · 2023Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Increased O-linked beta-N-acetylglucosamine (O-GlcNAc) is associated with insulin resistance in muscle and adipocytes. Upon insulin treatment of insulin-responsive adipocytes, O-GlcNAcylation of several proteins is increased. Key insulin signaling proteins, including IRS-1, IRS-2, and PDK1, are substrates for OGT, suggesting potential O-GlcNAc control points within the pathway. To elucidate the roles of O-GlcNAc in dampening insulin signaling (Vosseller, K., Wells, L., Lane, M. D., and Hart, G. W. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 5313-5318), we focused on the pathway upstream of AKT. Increasing O-GlcNAc in 3T3-L1 adipocytes decreases phosphoinositide 3-kinase (PI3K) interactions with both IRS-1 and IRS-2. Elevated O-GlcNAc also reduces phosphorylation of the PI3K p85 binding motifs (YXXM) of IRS-1 and results in a concomitant reduction in tyrosine phosphorylation of Y(608)XXM in IRS-1, one of the two main PI3K p85 binding motifs. Additionally, insulin signaling stimulates the interaction of OGT with PDK1. We conclude that one of the steps at which O-GlcNAc contributes to insulin resistance is by inhibiting phosphorylation at the Y(608)XXM PI3K p85 binding motif in IRS-1 and possibly at PDK1 as well.
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.