ArticleMolecular and cellular biochemistry2016
Sirtuin-3 (SIRT3) protects pancreatic β-cells from endoplasmic reticulum (ER) stress-induced apoptosis and dysfunction.
Article in Molecular and cellular biochemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Sirtuins as Molecular Mediators of Caloric Restriction in the Pancreas: Implications for β-Cell Function, Metabolism, and Longevity.International journal of molecular sciences · 2026Review
- 3-TYP protects against heart failure with preserved ejection fraction by inhibiting Sirtuin 3.Journal of molecular histology · 2025Article
- Annexin-A1 short peptide alleviates septic myocardial injury by upregulating SIRT3 and inhibiting myocardial cell apoptosis.Histology and histopathology · 2024Article
- Effect of Akkermansia muciniphila on pancreatic islet β-cell function in rats with prediabetes mellitus induced by a high-fat diet.Bioresources and bioprocessing · 2024Article
- Gene Expression Profiling Reveals Fundamental Sex-Specific Differences in SIRT3-Mediated Redox and Metabolic Signaling in Mouse Embryonic Fibroblasts.International journal of molecular sciences · 2024Article
- Epigenetic Regulation of Pancreas Development and Function.Advances in anatomy, embryology, and cell biology · 2024Review
- The mitochondrial unfolded protein response (UPRJournal of hematology & oncology · 2022Review
- SIRT3 inhibitor 3-TYP exacerbates thioacetamide-induced hepatic injury in mice.Frontiers in physiology · 2022Article
- Neuraminidase 1 deficiency attenuates cardiac dysfunction, oxidative stress, fibrosis, inflammatory via AMPK-SIRT3 pathway in diabetic cardiomyopathy mice.International journal of biological sciences · 2022Article
- Mitofusin2 PromotesStem cells international · 2022Article
- Article
- Review
- Therapeutic Role of Sirtuins Targeting Unfolded Protein Response, Coagulation, and Inflammation in Hypoxia-Induced Thrombosis.Frontiers in physiology · 2021Review
- Sirtuins and their Biological Relevance in Aging and Age-Related Diseases.Aging and disease · 2020Review
- Mesenchymal Stem Cells Attenuate Diabetic Lung Fibrosis via Adjusting Sirt3-Mediated Stress Responses in Rats.Oxidative medicine and cellular longevity · 2020Article
- ATF6 regulates the development of chronic pancreatitis by inducing p53-mediated apoptosis.Cell death & disease · 2019Article
- Oleic acid ameliorates palmitic acid-induced ER stress and inflammation markers in naive and cerulein-treated exocrine pancreas cells.Bioscience reports · 2019Article
- The association of calcium channel blockers with β-cell function in type 2 diabetic patients: A cross-sectional study.Journal of clinical hypertension (Greenwich, Conn.) · 2019Article
- Article
- TAK-875 MitigatesJournal of diabetes research · 2019Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Insufficient insulin produced by pancreatic β-cells in the control of blood sugar is a central feature of the etiology of diabetes. Reports have shown that endoplasmic reticulum (ER) stress is fundamentally involved in β-cell dysfunction. In this study, we hypothesized that NAD-dependent deacetylase sirtuin-3 (SIRT3), an important regulator of cell metabolism, protects pancreatic β-cells from ER stress-mediated apoptosis. To validate our hypothesis, a rat diabetic model was established by a high-fat diet (HFD). We found that SIRT3 expression was markedly decreased in NIT1 and INS1 cells incubated with palmitate. Palmitate treatment significantly decreased β-cell viability and insulin secretion, and promoted malondialdehyde (MDA) formation. However, SIRT3 overexpression in NIT1 and INS1 cells reversed these effects, resulting in higher insulin secretion, decreased β-cell apoptosis, and downregulation of the expression of ER stress-associated genes. Moreover, SIRT3 overexpression also inhibited calcium influx and the hyperacetylation of glucose-regulated protein of 78 kDa (GRP78). SIRT3 knockdown effectively enhanced the upregulation of phospho-extracellular regulated protein kinases (pERK), inositol-requiring enzyme-1 (IRE1), activating transcription factor 6 (ATF6), and C/EBP homologous protein (CHOP) induced by palmitate, and promoted palmitate-induced β-cell apoptosis and dysfunction. Taken together, our results suggest that SIRT3 is an integral regulator of ER function and that its depletion might result in the hyperacetylation of critical ER proteins that protect against islet lipotoxicity under conditions of nutrient excess.
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