ArticleDiabetes2011
Δ40 Isoform of p53 controls β-cell proliferation and glucose homeostasis in mice.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 55 citations in OpenAlex.
- Disruption of the ∆40p53/miR-4671-5p/SGSH axis results in intra-S-phase arrest and poor cancer prognosis.The FEBS journal · 2026Article
- The interplay of tumor suppressor p53 and oxidative stress in pancreatic β-cell apoptosis and insulin resistance in newly diagnosed type 2 diabetes mellitus.Diabetology & metabolic syndrome · 2025Article
- Pancreatic β-Cell Apoptosis in Normoglycemic Rats is Due to Mitochondrial Translocation of p53-Induced by the Consumption of Sugar-Sweetened Beverages.Cell biochemistry and biophysics · 2023Article
- The "LINC" between Δ40p53-miRNA Axis in the Regulation of Cellular Homeostasis.Molecular and cellular biology · 2023Article
- The Senescence Markers p16INK4A, p14ARF/p19ARF, and p21 in Organ Development and Homeostasis.Cells · 2022Review
- Identification of core genes associated with type 2 diabetes mellitus and gastric cancer by bioinformatics analysis.Annals of translational medicine · 2022Article
- Adaptive homeostasis and the p53 isoform network.EMBO reports · 2021Review
- Review
- Increased insulin sensitivity and diminished pancreatic beta-cell function in DNA repair deficient Ercc1Metabolism: clinical and experimental · 2021Article
- Review
- Sleeve gastrectomy ameliorates endothelial function and prevents lung cancer by normalizing endothelin-1 axis in obese and diabetic rats.World journal of gastroenterology · 2020Article
- Metabolic functions of the tumor suppressor p53: Implications in normal physiology, metabolic disorders, and cancer.Molecular metabolism · 2020Review
- The Emerging Landscape of p53 Isoforms in Physiology, Cancer and Degenerative Diseases.International journal of molecular sciences · 2019Review
- GScluster: network-weighted gene-set clustering analysis.BMC genomics · 2019Article
- Obesity, DNA Damage, and Development of Obesity-Related Diseases.International journal of molecular sciences · 2019Review
- Conformational stability and dynamics of the cancer-associated isoform Δ133p53β are modulated by p53 peptides and p53-specific DNA.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Length and secondary structure of the 5' non-coding regions of mouse p53 mRNA transcripts - mouse as a model organism for p53 gene expression studies.RNA biology · 2019Article
- Control of metabolism by p53 - Cancer and beyond.Biochimica et biophysica acta. Reviews on cancer · 2018Review
- Emerging Roles of p53 Family Members in Glucose Metabolism.International journal of molecular sciences · 2018Review
- Exploring the molecular mechanisms underlying α- and β-cell dysfunction in diabetes.Diabetology international · 2017Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
objectiveInvestigating the dynamics of pancreatic β-cell mass is critical for developing strategies to treat both type 1 and type 2 diabetes. p53, a key regulator of the cell cycle and apoptosis, has mostly been a focus of investigation as a tumor suppressor. Although p53 alternative transcripts can modulate p53 activity, their functions are not fully understood. We hypothesized that β-cell proliferation and glucose homeostasis were controlled by Δ40p53, a p53 isoform lacking the transactivation domain of the full-length protein that modulates total p53 activity and regulates organ size and life span in mice. RESEARCH DESIGN AND
methodsWe phenotyped metabolic parameters in Δ40p53 transgenic (p44tg) mice and used quantitative RT-PCR, Western blotting, and immunohistochemistry to examine β-cell proliferation.
resultsTransgenic mice with an ectopic p53 gene encoding Δ40p53 developed hypoinsulinemia and glucose intolerance by 3 months of age, which worsened in older mice and led to overt diabetes and premature death from ∼14 months of age. Consistent with a dramatic decrease in β-cell mass and reduced β-cell proliferation, lower expression of cyclin D2 and pancreatic duodenal homeobox-1, two key regulators of proliferation, was observed, whereas expression of the cell cycle inhibitor p21, a p53 target gene, was increased.
conclusionsThese data indicate a significant and novel role for Δ40p53 in β-cell proliferation with implications for the development of age-dependent diabetes.
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Registered trials
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