ArticleAmerican journal of physiology. Endocrinology and metabolism2013
Upregulation of p21 activates the intrinsic apoptotic pathway in β-cells.
Article in American journal of physiology. Endocrinology and metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Iron deficiency induces maturation-dependent loss of pancreatic β-cells.Nature communications · 2026Article
- Single-cell virtual knockout network perturbation prioritizes candidate regulators of beta-cell functional failure in type 2 diabetes.Frontiers in endocrinology · 2026Article
- Lipin3 deficiency aggravates cisplatin induced acute kidney injury via activating Sirt1-p21-Caspase 3-GSDME pyroptosis pathway.International journal of biological sciences · 2025Article
- The Emerging Role of p21 in Diabetes and Related Metabolic Disorders.International journal of molecular sciences · 2024Review
- Dihydroartemisinin Enhances the Therapeutic Efficacy of BH3 Mimetic Inhibitor in Acute Lymphoblastic Leukemia Cells via Inhibition of Mcl-1.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Enhancement of the Sensitivity of the Acute Lymphoblastic Leukemia Cells to ABT-737 by Formononetin.International journal of molecular and cellular medicine · 2024Article
- Accelerated Senescence and Apoptosis in the Rat Liver during the Progression of Diabetic Complications.The Malaysian journal of medical sciences : MJMS · 2022Article
- Endocannabinoid System and Tumour Microenvironment: New Intertwined Connections for Anticancer Approaches.Cells · 2021Review
- Interrogation of novel CDK2/9 inhibitor fadraciclib (CYC065) as a potential therapeutic approach for AML.Cell death discovery · 2021Article
- The Fate Status of Stem Cells in Diabetes and its Role in the Occurrence of Diabetic Complications.Frontiers in molecular biosciences · 2021Review
- Calcium Entry through TRPV1: A Potential Target for the Regulation of Proliferation and Apoptosis in Cancerous and Healthy Cells.International journal of molecular sciences · 2020Review
- Increased double strand breaks in diabetic β-cells with a p21 response that limits apoptosis.Scientific reports · 2019Article
- STK38L kinase ablation promotes loss of cell viability in a subset of KRAS-dependent pancreatic cancer cell lines.Oncotarget · 2017Article
- Is p53 Involved in Tissue-Specific Insulin Resistance Formation?Oxidative medicine and cellular longevity · 2017Review
- Ciclopirox enhances pancreatic islet health by modulating the unfolded protein response in diabetes.Pflugers Archiv : European journal of physiology · 2016Article
- Deletion of β-Arrestin2 in Mice Limited Pancreatic β-Cell Expansion under Metabolic Stress through Activation of the JNK Pathway.Molecular medicine (Cambridge, Mass.) · 2016Article
- Differential influence of tacrolimus and sirolimus on mitochondrial-dependent signaling for apoptosis in pancreatic cells.Molecular and cellular biochemistry · 2016Article
- EBNA3C augments Pim-1 mediated phosphorylation and degradation of p21 to promote B-cell proliferation.PLoS pathogens · 2014Article
- Androgen receptor-mediated apoptosis in bovine testicular induced pluripotent stem cells in response to phthalate esters.Cell death & disease · 2013Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Diabetes manifests from a loss in functional β-cell mass, which is regulated by a dynamic balance of various cellular processes, including β-cell growth, proliferation, and death as well as secretory function. The cell cycle machinery comprised of cyclins, kinases, and inhibitors regulates proliferation. However, their involvement during β-cell stress during the development of diabetes is not well understood. Interestingly, in a screen of multiple cell cycle inhibitors, p21 was dramatically upregulated in INS-1-derived 832/13 cells and rodent islets by two pharmacological inducers of β-cell stress, dexamethasone and thapsigargin. We hypothesized that β-cell stress upregulates p21 to activate the apoptotic pathway and suppress cell survival signaling. To this end, p21 was adenovirally overexpressed in pancreatic rat islets and 832/13 cells. As expected, p21 overexpression resulted in decreased [(3)H]thymidine incorporation. Flow cytometry analysis in p21-transduced 832/13 cells verified lower replication, as indicated by a decreased cell population in the S phase and a block in G2/M transition. The sub-G0 cell population was higher with p21 overexpression and was attributable to apoptosis, as demonstrated by increased annexin-positive stained cells and cleaved caspase-3 protein. p21-mediated caspase-3 cleavage was inhibited by either overexpression of the antiapoptotic mitochondrial protein Bcl-2 or siRNA-mediated suppression of the proapoptotic proteins Bax and Bak. Therefore, an intact intrinsic apoptotic pathway is central for p21-mediated cell death. In summary, our findings indicate that β-cell apoptosis can be triggered by p21 during stress and is thus a potential target to inhibit for protection of functional β-cell mass.
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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.