ArticlePloS one2018
SIRT2 knockout exacerbates insulin resistance in high fat-fed mice.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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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.
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Who cites it
36 citing papers in PubMed, 57 citations in OpenAlex.
- Review
- Exercise and the hepatic sirtuin network: rethinking the research focus on SIRT1, SIRT3, and SIRT6.Frontiers in physiology · 2026Article
- Untargeted metabolomic and proteomic analysis implicates SIRT2 as a novel therapeutic target for diabetic nephropathy.Scientific reports · 2025Article
- Mitochondrial SIRT2-mediated CPT2 deacetylation prevents diabetic cardiomyopathy by impeding cardiac fatty acid oxidation.International journal of biological sciences · 2025Article
- Discovery of Novel Thiazole-Based SIRT2 Inhibitors as Anticancer Agents: Molecular Modeling, Chemical Synthesis and Biological Assays.International journal of molecular sciences · 2024Article
- Drugs Targeting Sirtuin 2 Exhibit Broad-Spectrum Anti-Infective Activity.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Sirt2 Regulates Liver Metabolism in a Sex-Specific Manner.Biomolecules · 2024Article
- Loss of NAMPT and SIRT2 but not SIRT1 attenuate GLO1 expression and activity in human skeletal muscle.Redox biology · 2024Article
- The role of NAD-dependent deacetylase sirtuin-2 in liver metabolic stress through regulating pyruvate kinase M2 ubiquitination.Journal of translational medicine · 2024Article
- Deciphering the role of alternative splicing as a potential regulator in fat-tail development of sheep: a comprehensive RNA-seq based study.Scientific reports · 2024Review
- Effects of Fasting on Metabolic Hormones and Functions: A Narrative Review.Juntendo Iji zasshi = Juntendo medical journal · 2024Review
- Unlocking the Nexus of Sirtuins: A Comprehensive Review of Their Role in Skeletal Muscle Metabolism, Development, and Disorders.International journal of biological sciences · 2024Review
- Frequency of the rs2015 (T>G) and rs2241703 (G>A) polymorphisms in the miRNA-SIRT2 gene in type 2 diabetes mellitus in Saudi Arabia.Saudi medical journal · 2023Article
- Histone Deacetylases: Molecular Mechanisms and Therapeutic Implications for Muscular Dystrophies.International journal of molecular sciences · 2023Review
- Histone deacetylase functions and therapeutic implications for adult skeletal muscle metabolism.Frontiers in molecular biosciences · 2023Review
- The epigenetic regulatory effect of histone acetylation and deacetylation on skeletal muscle metabolism-a review.Frontiers in physiology · 2023Review
- Sirtuins in atherosclerosis: guardians of healthspan and therapeutic targets.Nature reviews. Cardiology · 2022Review
- Mapping endocrine networks by stable isotope tracing.Current opinion in endocrine and metabolic research · 2022Review
- Improvement in insulin sensitivity and prevention of high fat diet-induced liver pathology using a CXCR2 antagonist.Cardiovascular diabetology · 2022Article
- SIRT2 Deficiency Exacerbates Hepatic Steatosis via a Putative Role of the ER Stress Pathway.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The NAD+-dependent deacetylase SIRT2 is unique amongst sirtuins as it is effective in the cytosol, as well as the mitochondria. Defining the role of cytosolic acetylation state in specific tissues is difficult since even physiological effects at the whole body level are unknown. We hypothesized that genetic SIRT2 knockout (KO) would lead to impaired insulin action, and that this impairment would be worsened in HF fed mice. Insulin sensitivity was tested using the hyperinsulinemic-euglycemic clamp in SIRT2 KO mice and WT littermates. SIRT2 KO mice exhibited reduced skeletal muscle insulin-induced glucose uptake compared to lean WT mice, and this impairment was exacerbated in HF SIRT2 KO mice. Liver insulin sensitivity was unaffected in lean SIRT2 KO mice. However, the insulin resistance that accompanies HF-feeding was worsened in SIRT2 KO mice. It was notable that the effects of SIRT2 KO were largely disassociated from cytosolic acetylation state, but were closely linked to acetylation state in the mitochondria. SIRT2 KO led to an increase in body weight that was due to increased food intake in HF fed mice. In summary, SIRT2 deletion in vivo reduces muscle insulin sensitivity and contributes to liver insulin resistance by a mechanism that is unrelated to cytosolic acetylation state. Mitochondrial acetylation state and changes in feeding behavior that result in increased body weight correspond to the deleterious effects of SIRT2 KO on insulin action.
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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.