ArticleDiabetes2015
Sestrin 3 protein enhances hepatic insulin sensitivity by direct activation of the mTORC2-Akt signaling.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
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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.
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
62 citing papers in PubMed, 92 citations in OpenAlex.
- Leucine Enhances Stress Resistance in Honeybees (Biology · 2026Article
- Mechanisms of Protection Against Oxidative Stress During Hibernation.International journal of molecular sciences · 2026Review
- The mTOR Pathway in Hearing Disorders: Mechanistic Links to Aging, Regeneration, and Neurodegeneration.Molecular neurobiology · 2026Review
- Unlocking the benefits of aerobic exercise for MAFLD: a comprehensive mechanistic analysis.Journal of translational medicine · 2025Review
- Sestrins: a new therapeutic target for endothelial dysfunction and cardiovascular disease prevention.Annals of medicine · 2025Review
- Sestrin2 is Induced Upon Cellular Stress but Has No Effect on Myotube Size or Amino Acid Sensing in C2C12 Myotubes.Biology of the cell · 2025Article
- Beckwith-Wiedemann syndrome and large offspring syndrome involve alterations in methylome, transcriptome, and chromatin configuration.NAR molecular medicine · 2025Article
- Potential Role of SESN3 in Linking Heart Failure with Preserved Ejection Fraction and Chronic Obstructive Pulmonary Disease via Autophagy Dysregulation.International journal of molecular sciences · 2025Article
- Restoration of Sestrin 3 Expression Mitigates Cardiac Oxidative Damage in Ischemia-Reperfusion Injury Model.Antioxidants (Basel, Switzerland) · 2025Article
- Tanycytes from a bird's eye view: gene expression profiling of the tanycytic region under different seasonal states in the Svalbard ptarmigan.Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology · 2025Article
- Role of sestrins in metabolic and aging-related diseases.Biogerontology · 2024Review
- Sestrin1, 2, and 3 are dispensable for female fertility in mice.Journal of ovarian research · 2024Article
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- Antioxidant genes in cancer and metabolic diseases: Focusing on Nrf2, Sestrin, and heme oxygenase 1.International journal of biological sciences · 2024Review
- Glucose-Induced Activation of mTORC1 is Associated with Hexokinase2 Binding to Sestrins in HEK293T Cells.The Journal of nutrition · 2023Article
- Specificity and sensitivity of the SeLECT score in predicting late seizures in patients undergoing intravenous thrombolytic treatment and the effect of diabetes mellitus and leukoaraiosis.Arquivos de neuro-psiquiatria · 2023Article
- Immunoregulation: the interplay between metabolism and redox homeostasis.Frontiers in transplantation · 2023Review
- The central moTOR of metabolism.Developmental cell · 2022Review
- Exploring New Drug Targets for Type 2 Diabetes: Success, Challenges and Opportunities.Biomedicines · 2022Review
- The functions and roles of sestrins in regulating human diseases.Cellular & molecular biology letters · 2022Review
2 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
4 authors at 2 institutions in 1 country.
Funding
Abstract
Sestrin proteins have been implicated in multiple biological processes including resistance to oxidative and genotoxic stresses, protection against aging-related pathologies, and promotion of metabolic homeostasis; however, the underlying mechanisms are incompletely understood. Some evidence suggests that sestrins may inhibit mTORC1 (mechanistic target of rapamycin complex 1) through inhibition of RagA/B GTPases or activation of AMPK; however, whether sestrins are also involved in mTORC2 regulation and function is unclear. To investigate the functions and mechanisms of Sestrin 3 (Sesn3), we generated Sesn3 liver-specific transgenic and knockout mice. Our data show that Sesn3 liver-specific knockout mice exhibit insulin resistance and glucose intolerance, and Sesn3 transgenic mice were protected against insulin resistance induced by a high-fat diet. Using AMPK liver-specific knockout mice, we demonstrate that the Sesn3 insulin-sensitizing effect is largely independent of AMPK. Biochemical analysis reveals that Sesn3 interacts with and activates mTORC2 and subsequently stimulates Akt phosphorylation at Ser473. These findings suggest that Sesn3 can activate Akt via mTORC2 to regulate hepatic insulin sensitivity and glucose metabolism.
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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.