ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
Hepatic overexpression of SIRT1 in mice attenuates endoplasmic reticulum stress and insulin resistance in the liver.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers.
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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.
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Who cites it
158 citing papers in PubMed, 291 citations in OpenAlex.
- Trial
- Tunicamycin-induced ER stress promotes inflammation in SH-SY5Y cells through ROS-NF-κB-SIRT1 pathway.Molecular biology reports · 2026Article
- SETDB1 promotes gastric cancer progression via UPR and mTOR pathway.Cancer cell international · 2026Article
- Running out the clock: Circadian rhythm dysfunction in cognitive disease.International review of neurobiology · 2026Review
- Modulation of Endoplasmic Reticulum Stress by Selected Polyphenols fromPlants (Basel, Switzerland) · 2025Review
- Association ofHealth science reports · 2025Article
- The clinical value of serum sirtuin-1 concentration in the diagnosis of metabolic dysfunction-associated steatotic liver disease.BMC gastroenterology · 2025Article
- Cardiovascular and nonalcoholic fatty liver disease: Sharing common ground through SIRT1 pathways.World journal of cardiology · 2024Review
- Saikogenin A improves ethanol-induced liver injury by targeting SIRT1 to modulate lipid metabolism.Communications biology · 2024Article
- Exploring histone deacetylases in type 2 diabetes mellitus: pathophysiological insights and therapeutic avenues.Clinical epigenetics · 2024Review
- Combined Administration of Metformin and Vitamin D: A Futuristic Approach for Management of Hyperglycemia.Cardiovascular & hematological agents in medicinal chemistry · 2024Review
- SIRT1 exerts protective effects by inhibiting endoplasmic reticulum stress and NF-κB signaling pathways.Frontiers in cell and developmental biology · 2024Review
- Review
- The Crosstalk between Mesenchymal Stromal/Stem Cells and Hepatocytes in Homeostasis and under Stress.International journal of molecular sciences · 2023Review
- Age-dependent loss of hepatic SIRT1 enhances NLRP3 inflammasome signaling and impairs capacity for liver fibrosis resolution.Aging cell · 2023Article
- Antidiabetic activity ofFrontiers in pharmacology · 2023Article
- Genetic Variants ofInternational journal of endocrinology · 2023Article
- Sirtuin 1 alleviates alcoholic liver disease by inhibiting HMGB1 acetylation and translocation.PeerJ · 2023Article
- FoxO1 as a tissue-specific therapeutic target for type 2 diabetes.Frontiers in endocrinology · 2023Review
- Circadian Clock Desynchronization and Insulin Resistance.International journal of environmental research and public health · 2022Review
98 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
12 authors at 3 institutions in 1 country.
Funding
Abstract
Endoplasmic reticulum (ER) stress has been implicated in the pathophysiology of human type 2 diabetes (T2DM). Although SIRT1 has a therapeutic effect on metabolic deterioration in T2DM, the precise mechanisms by which SIRT1 improves insulin resistance remain unclear. Here, we demonstrate that adenovirus-mediated overexpression of SIRT1 in the liver of diet-induced insulin-resistant low-density lipoprotein receptor-deficient mice and of genetically obese ob/ob mice attenuates hepatic steatosis and ameliorates systemic insulin resistance. These beneficial effects were associated with decreased mammalian target of rapamycin complex 1 (mTORC1) activity, inhibited the unfolded protein response (UPR), and enhanced insulin receptor signaling in the liver, leading to decreased hepatic gluconeogenesis and improved glucose tolerance. The tunicamycin-induced splicing of X-box binding protein-1 and expression of GRP78 and CHOP were reduced by resveratrol in cultured cells in a SIRT1-dependent manner. Conversely, SIRT1-deficient mouse embryonic fibroblasts challenged with tunicamycin exhibited markedly increased mTORC1 activity and impaired ER homeostasi and insulin signaling. These effects were abolished by mTORC1 inhibition by rapamycin in human HepG2 cells. These studies indicate that SIRT1 serves as a negative regulator of UPR signaling in T2DM and that SIRT1 attenuates hepatic steatosis, ameliorates insulin resistance, and restores glucose homeostasis, largely through the inhibition of mTORC1 and ER stress.
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What OpenQuestion holds
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.