ArticleScientific reports2019
Increased double strand breaks in diabetic β-cells with a p21 response that limits apoptosis.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Pancreatic β-cell aging in physiology and diabetes: emerging roles of m6A mRNA methylation.Journal of molecular endocrinology · 2026Review
- Nucleolar stress facilitates islet β cell senescence via hijacking the DNA damage response pathways.iScience · 2025Article
- Dynamic properties of enhancer and promoter during DNA damage in hepatocellular carcinoma.iScience · 2025Article
- Article
- The Emerging Role of p21 in Diabetes and Related Metabolic Disorders.International journal of molecular sciences · 2024Review
- Exploring Transcriptional Regulation of Beta Cell SASP by Brd4-Associated Proteins and Cell Cycle Control Protein p21.Epigenomes · 2024Article
- The Perfect Cup? Coffee-Derived Polyphenols and Their Roles in Mitigating Factors Affecting Type 2 Diabetes Pathogenesis.Molecules (Basel, Switzerland) · 2024Review
- Epigenetic Regulation of Pancreas Development and Function.Advances in anatomy, embryology, and cell biology · 2024Review
- p21 promotes gemcitabine tolerance in A549 cells by inhibiting DNA damage and altering the cell cycle.Oncology letters · 2023Article
- Obesity promotes breast epithelium DNA damage in women carrying a germline mutation inScience translational medicine · 2023Article
- Failure to repair endogenous DNA damage in β-cells causes adult-onset diabetes in mice.Aging biology · 2023Article
- Pancreatic β-cell senescence in diabetes: mechanisms, markers and therapies.Frontiers in endocrinology · 2023Review
- The Transcription Factor YY1 Is Essential for Normal DNA Repair and Cell Cycle in Human and Mouse β-Cells.Diabetes · 2022Article
- Proteins from the DNA Damage Response: Regulation, Dysfunction, and Anticancer Strategies.Cancers · 2021Review
- A set of miRNAs predicts T2DM remission in patients with coronary heart disease: from the CORDIOPREV study.Molecular therapy. Nucleic acids · 2021Article
- Coping with DNA Double-Strand Breaks via ATM Signaling Pathway in Bovine Oocytes.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA damage and DNA damage response (DDR) pathways in β-cells have received little attention especially in the context of type-2 diabetes. We postulate that p21 plays a key role in DDR by preventing apoptosis, associated through its overexpression triggered by DNA stand breaks (DSBs). Our results show that β-cells from chronic diabetic mice had a greater extent of DSBs as compared to their non-diabetic counterparts. Comet assays and nuclear presence of γH2AX and 53bp1 revealed increased DNA DSBs in 16 weeks old (wo) db/db β-cells as compared to age matched non-diabetic β-cells. Our study of gene expression changes in MIN6 cell line with doxorubicin (Dox) induced DNA damage, showed that the DDR was similar to primary β-cells from diabetic mice. There was significant overexpression of DDR genes, gadd45a and p21 after a 24-hr treatment. Western blot analysis revealed increased cleaved caspase3 over time, suggesting higher frequency of apoptosis due to Dox-induced DNA strand breaks. Inhibition of p21 by pharmacological inhibitor UC2288 under DNA damage conditions (both in Dox-induced MIN6 cells and older db/db islets) significantly increased the incidence of β-cell apoptosis. Our studies confirmed that while DNA damage, specifically DSBs, induced p21 overexpression in β-cells and triggered the p53/p21 cellular response, p21 inhibition exacerbated the frequency of apoptosis.
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