ArticleThe Journal of biological chemistry2008
Elevation of global O-GlcNAc levels in 3T3-L1 adipocytes by selective inhibition of O-GlcNAcase does not induce insulin resistance.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 120 citations in OpenAlex.
- Semaglutide Alleviates LPS-Induced Cognitive Disorder via O-GlcNAcylation of AKT-mTOR Signaling Pathway Components.Neuromolecular medicine · 2026Article
- Emerging gut microbial glycoside hydrolase inhibitors.RSC chemical biology · 2025Review
- O-GlcNAcylation in Endocrinology: The Sweet Link.Endocrinology · 2025Review
- 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
- O-GlcNAcylation of MITF regulates its activity and CDK4/6 inhibitor resistance in breast cancer.Nature communications · 2024Article
- NButGT Reinforces the Beneficial Effects of Epinephrine on Cardiac Mitochondrial Respiration, Lactatemia and Cardiac Output in Experimental Anaphylactic Shock.International journal of molecular sciences · 2024Article
- Understanding and exploiting the roles of O-GlcNAc in neurodegenerative diseases.The Journal of biological chemistry · 2023Review
- Article
- Posttranslational modifications in diabetes: Mechanisms and functions.Reviews in endocrine & metabolic disorders · 2022Review
- Protein O-GlcNAcylation and the regulation of energy homeostasis: lessons from knock-out mouse models.Journal of biomedical science · 2022Review
- The intra-mitochondrial O-GlcNAcylation system rapidly modulates OXPHOS function and ROS release in the heart.Communications biology · 2022Article
- Review
- Insulin Resistance: From Mechanisms to Therapeutic Strategies.Diabetes & metabolism journal · 2022Review
- Mechanistic roles for altered O-GlcNAcylation in neurodegenerative disorders.The Biochemical journal · 2021Review
- Role ofPhysiological reviews · 2021Review
- Role of the O-GlcNAc modification on insulin resistance and endoplasmic reticulum stress in 3T3-L1 cells.Molecular biology reports · 2020Article
- Regulation of cardiac O-GlcNAcylation: More than just nutrient availability.Biochimica et biophysica acta. Molecular basis of disease · 2020Review
- Computational Studies on the Potency and Selectivity of PUGNAc Derivatives Against GH3, GH20, and GH84 β-N-acetyl-D-hexosaminidases.Frontiers in chemistry · 2019Article
- Critical observations that shaped our understanding of the function(s) of intracellular glycosylation (O-GlcNAc).FEBS letters · 2018Review
9 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The O-GlcNAc post-translational modification is considered to act as a sensor of nutrient flux through the hexosamine biosynthetic pathway. A cornerstone of this hypothesis is that global elevation of protein O-GlcNAc levels, typically induced with the non-selective O-GlcNAcase inhibitor PUGNAc (O-(2-acetamido-2-deoxy-D-glycopyranosylidene) amino-N-phenylcarbamate), causes insulin resistance in adipocytes. Here we address the potential link between elevated O-GlcNAc and insulin resistance by using a potent and selective inhibitor of O-GlcNAcase (NButGT (1,2-dideoxy-2'-propyl-alpha-D-glucopyranoso-[2,1-D]-Delta 2'-thiazoline), 1200-fold selectivity). A comparison of the structures of a bacterial homologue of O-GlcNAcase in complex with PUGNAc or NButGT reveals that these inhibitors bind to the same region of the active site, underscoring the competitive nature of their inhibition of O-GlcNAcase and the molecular basis of selectivity. Treating 3T3-L1 adipocytes with NButGT induces rapid increases in global O-GlcNAc levels, but strikingly, NButGT treatment does not replicate the insulin desensitizing effects of the non-selective O-GlcNAcase inhibitor PUGNAc. Consistent with these observations, NButGT also does not recapitulate the impaired insulin-mediated phosphorylation of Akt that is induced by treatment with PUGNAc. Collectively, these results suggest that increases in global levels of O-GlcNAc-modified proteins of cultured adipocytes do not, on their own, cause insulin resistance.
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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.