ArticleDiabetologia2013
The loss of Sirt1 in mouse pancreatic beta cells impairs insulin secretion by disrupting glucose sensing.
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 79 citations in OpenAlex.
- Trial
- Nutrition, Circadian Regulation, and the Gut-Melatonin-Visceral Adipose Tissue Axis: An Integrative Narrative Review.Nutrients · 2026Review
- Review
- Placenta-derived small extracellular vesicles transfer miR-520d-5p to mediate pancreatic β-cell injury in gestational diabetes mellitus by targeting SIRT1.BMC pregnancy and childbirth · 2026Article
- The clinical value of serum sirtuin-1 concentration in the diagnosis of metabolic dysfunction-associated steatotic liver disease.BMC gastroenterology · 2025Article
- Nicotinamide Mononucleotide (NMN) Ameliorates Free Fatty Acid-Induced Pancreatic β-Cell Dysfunction via the NADInternational journal of molecular sciences · 2024Article
- Mesenchymal stromal cells ameliorate mitochondrial dysfunction in α cells and hyperglucagonemia in type 2 diabetes via SIRT1/FoxO3a signaling.Stem cells translational medicine · 2024Article
- Long-Term Administration of Omeprazole-Induced Hypergastrinemia and Changed Glucose Homeostasis and Expression of Metabolism-Related Genes.BioMed research international · 2024Article
- Type 2 diabetes candidate genes, including PAX5, cause impaired insulin secretion in human pancreatic islets.The Journal of clinical investigation · 2023Article
- Regulation of insulin secretion by the post-translational modifications.Frontiers in cell and developmental biology · 2023Review
- Genetic Variants ofInternational journal of endocrinology · 2023Article
- Non-coding variants disrupting a tissue-specific regulatory element in HK1 cause congenital hyperinsulinism.Nature genetics · 2022Article
- 12/15-Lipoxygenase Regulation of Diabetic Cognitive Dysfunction Is Determined by Interfering with Inflammation and Cell Apoptosis.International journal of molecular sciences · 2022Article
- Hippocampal insulin resistance and the Sirtuin 1 signaling pathway in diabetes-induced cognitive dysfunction.Neural regeneration research · 2021Article
- Vascepa protects against high-fat diet-induced glucose intolerance, insulin resistance, and impaired β-cell function.iScience · 2021Article
- Review
- SIRT2 ablation inhibits glucose-stimulated insulin secretion through decreasing glycolytic flux.Theranostics · 2021Article
- The Regulatory Effect of SIRT1 on Extracellular Microenvironment Remodeling.International journal of biological sciences · 2021Review
- Sirt1-PPARS Cross-Talk in Complex Metabolic Diseases and Inherited Disorders of the One Carbon Metabolism.Cells · 2020Review
- SIRT1 Activation byMolecules (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
aims/hypothesisSirtuin 1 (SIRT1) has emerged as a key metabolic regulator of glucose homeostasis and insulin secretion. Enhanced SIRT1 activity has been shown to be protective against diabetes, although the mechanisms remain largely unknown. The aim of this study was to determine how SIRT1 regulates insulin secretion in the pancreatic beta cell.
methodsPancreatic beta cell-specific Sirt1 deletion was induced by tamoxifen injection in 9-week-old Pdx1CreER:floxSirt1 mice (Sirt1BKO). Controls were injected with vehicle. Mice were assessed metabolically via glucose challenge, insulin tolerance tests and physical variables. In parallel, Sirt1 short interfering RNA-treated MIN6 cells (SIRT1KD) and isolated Sirt1BKO islets were used to investigate the effect of SIRT1 inactivation on insulin secretion and gene expression.
resultsOGTTs showed impaired glucose disposal in Sirt1BKO mice due to insufficient insulin secretion. Isolated Sirt1BKO islets and SIRT1KD MIN6 cells also exhibited impaired glucose-stimulated insulin secretion. Subsequent analyses revealed impaired α-ketoisocaproic acid-induced insulin secretion and attenuated glucose-induced Ca(2+) influx, but normal insulin granule exocytosis in Sirt1BKO beta cells. Microarray studies revealed a large cluster of mitochondria-related genes, the expression of which was dysregulated in SIRT1KD MIN6 cells. Upon further analysis, we demonstrated an explicit defect in mitochondrial function: the inability to couple nutrient metabolism to mitochondrial membrane hyperpolarisation and reduced oxygen consumption rates. CONCLUSIONS/
interpretationTaken together, these findings indicate that in beta cells the deacetylase SIRT1 regulates the expression of specific mitochondria-related genes that control metabolic coupling, and that a decrease in beta cell Sirt1 expression impairs glucose sensing and insulin secretion.
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