ArticleThe Journal of biological chemistry2015
Acetylation of TUG protein promotes the accumulation of GLUT4 glucose transporters in an insulin-responsive intracellular compartment.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 60 citations in OpenAlex.
- Altered Molecular Regulation of TUG Is a Central Feature of Insulin-Resistant Human Adipose Tissue.Diabetes · 2026Article
- GLUT4 Trafficking and Storage Vesicles: Molecular Architecture, Regulatory Networks, and Their Disruption in Insulin Resistance.International journal of molecular sciences · 2025Review
- TUG protein acts through a disordered region to organize the early secretory pathway.Nature communications · 2025Article
- VGF and the VGF-derived peptide AQEE30 stimulate osteoblastic bone formation through the C3a receptor.Experimental & molecular medicine · 2025Article
- Sirtuins and Their Implications in the Physiopathology of Gestational Diabetes Mellitus.Pharmaceuticals (Basel, Switzerland) · 2025Review
- UBXN9 governs GLUT4-mediated spatial confinement of RIG-I-like receptors and signaling.Nature immunology · 2024Article
- Microtubule-mediated GLUT4 trafficking is disrupted in insulin-resistant skeletal muscle.eLife · 2023Article
- ACBD3 Bioinformatic Analysis and Protein Expression in Breast Cancer Cells.International journal of molecular sciences · 2022Article
- Review
- p300 or CBP is required for insulin-stimulated glucose uptake in skeletal muscle and adipocytes.JCI insight · 2022Article
- Ubiquitin-like processing of TUG proteins as a mechanism to regulate glucose uptake and energy metabolism in fat and muscle.Frontiers in endocrinology · 2022Review
- Neuregulin 4 Downregulation Induces Insulin Resistance in 3T3-L1 Adipocytes through Inflammation and Autophagic Degradation of GLUT4 Vesicles.International journal of molecular sciences · 2021Article
- Insulin-stimulated endoproteolytic TUG cleavage links energy expenditure with glucose uptake.Nature metabolism · 2021Article
- Resveratrol Affects Insulin Signaling in Type 2 Diabetic Goto-Kakizaki Rats.International journal of molecular sciences · 2021Article
- Sirtuin 2 (SIRT2): Confusing Roles in the Pathophysiology of Neurological Disorders.Frontiers in neuroscience · 2021Review
- SIRT2 ablation inhibits glucose-stimulated insulin secretion through decreasing glycolytic flux.Theranostics · 2021Article
- Acute inhibition of protein deacetylases does not impact skeletal muscle insulin action.American journal of physiology. Cell physiology · 2019Article
- GLUT4 Storage Vesicles: Specialized Organelles for Regulated Trafficking.The Yale journal of biology and medicine · 2019Review
- Activator of one protease transforms into inhibitor of another in response to nutritional signals.Genes & development · 2019Article
- Germline or inducible knockout of p300 or CBP in skeletal muscle does not alter insulin sensitivity.American journal of physiology. Endocrinology and metabolism · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Insulin causes the exocytic translocation of GLUT4 glucose transporters to stimulate glucose uptake in fat and muscle. Previous results support a model in which TUG traps GLUT4 in intracellular, insulin-responsive vesicles termed GLUT4 storage vesicles (GSVs). Insulin triggers TUG cleavage to release the GSVs; GLUT4 then recycles through endosomes during ongoing insulin exposure. The TUG C terminus binds a GSV anchoring site comprising Golgin-160 and possibly other proteins. Here, we report that the TUG C terminus is acetylated. The TUG C-terminal peptide bound the Golgin-160-associated protein, ACBD3 (acyl-CoA-binding domain-containing 3), and acetylation reduced binding of TUG to ACBD3 but not to Golgin-160. Mutation of the acetylated residues impaired insulin-responsive GLUT4 trafficking in 3T3-L1 adipocytes. ACBD3 overexpression enhanced the translocation of GSV cargos, GLUT4 and insulin-regulated aminopeptidase (IRAP), and ACBD3 was required for intracellular retention of these cargos in unstimulated cells. Sirtuin 2 (SIRT2), a NAD(+)-dependent deacetylase, bound TUG and deacetylated the TUG peptide. SIRT2 overexpression reduced TUG acetylation and redistributed GLUT4 and IRAP to the plasma membrane in 3T3-L1 adipocytes. Mutation of the acetylated residues in TUG abrogated these effects. In mice, SIRT2 deletion increased TUG acetylation and proteolytic processing. During glucose tolerance tests, glucose disposal was enhanced in SIRT2 knock-out mice, compared with wild type controls, without any effect on insulin concentrations. Together, these data support a model in which TUG acetylation modulates its interaction with Golgi matrix proteins and is regulated by SIRT2. Moreover, acetylation of TUG enhances its function to trap GSVs within unstimulated cells and enhances insulin-stimulated glucose uptake.
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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.