ArticleScientific reports2017
Sirtinol promotes PEPCK1 degradation and inhibits gluconeogenesis by inhibiting deacetylase SIRT2.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 254 citations in OpenAlex.
- Inhibiting sirtuin-dependent DNA repair and oxidative stress responses impairs DIPG cell survival.Research square · 2025Article
- Dinochromosome Heterotermini with Telosomal Anchorages.International journal of molecular sciences · 2024Article
- Sirt2 Regulates Liver Metabolism in a Sex-Specific Manner.Biomolecules · 2024Article
- Emerging role of liver-bone axis in osteoporosis.Journal of orthopaedic translation · 2024Review
- Epigenome-metabolism nexus in the retina: implications for aging and disease.Trends in genetics : TIG · 2024Review
- Exploring histone deacetylases in type 2 diabetes mellitus: pathophysiological insights and therapeutic avenues.Clinical epigenetics · 2024Review
- Machine learning models to predict ligand binding affinity for the orexin 1 receptor.Artificial intelligence chemistry · 2024Article
- Pyruvate kinase is post-translationally regulated by sirtuin 2 in Aedes aegypti mosquitoes.Insect biochemistry and molecular biology · 2023Article
- PGAM5 deacetylation mediated by SIRT2 facilitates lipid metabolism and liver cancer proliferation.Acta biochimica et biophysica Sinica · 2023Article
- TRIM21 ameliorates hepatic glucose and lipid metabolic disorders in type 2 diabetes mellitus by ubiquitination of PEPCK1 and FASN.Cellular and molecular life sciences : CMLS · 2023Article
- High-resolution 3D X-ray diffraction microscopy: 3D mapping of deformed metal microstructures.Journal of applied crystallography · 2022Article
- Octanoic Acid-An Insecticidal Metabolite ofInternational journal of molecular sciences · 2022Article
- Sirtinol Supresses Trophozoites Proliferation and Encystation of Acanthamoeba via Inhibition of Sirtuin Family Protein.The Korean journal of parasitology · 2022Article
- Will Sirtuin 2 Be a Promising Target for Neuroinflammatory Disorders?Frontiers in cellular neuroscience · 2022Review
- Multiple Roles of SIRT2 in Regulating Physiological and Pathological Signal Transduction.Genetics research · 2022Review
- SL010110, a lead compound, inhibits gluconeogenesis via SIRT2-p300-mediated PEPCK1 degradation and improves glucose homeostasis in diabetic mice.Acta pharmacologica Sinica · 2021Article
- Dodecanol, metabolite of entomopathogenic fungus Conidiobolus coronatus, affects fatty acid composition and cellular immunity of Galleria mellonella and Calliphora vicina.Scientific reports · 2021Article
- Review
- The Role of Sirtuins in Kidney Diseases.International journal of molecular sciences · 2020Review
- Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphoenolpyruvate carboxykinase 1 (PEPCK1) is the critical enzyme for gluconeogenesis and is linked with type II diabetes. Previous studies have found that SIRT2, a deacetylase, plays an important role in deacetylating PEPCK1 and little is known about the anti-diabetic activity of SIRT2 inhibitors. In this study, we investigated the anti-diabetic effects of sirtinol, a SIRT2 inhibitor, on cell gluconeogenesis in vivo and in vitro. Immunoblotting analysis revealed that sirtinol significantly decreased the protein level of PEPCK1, and was accompanied by the hyperacetylation of PEPCK1 as well as decreased glucose output in a dose-dependent manner. Furthermore, sirtinol exerted little impact on endogenous PEPCK1 levels in SIRT2-knockdown cells. The in vitro experiments further confirmed the in vivo data; sirtinol decreased liver PEPCK1 protein level and prevented pyruvate-induced blood glucose from increasing. Based on our results, the rate-limiting enzyme PEPCK1 is the primary target of sirtinol, and the inhibition of SIRT2 activity may play an important role in cell gluconeogenesis. Thus, SIRT2 may be a novel molecular target for diabetes therapy and may thus shed light on the underlying diabetes treatment mechanisms of sirtinol.
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