ArticleNature medicine2016
p16(Ink4a)-induced senescence of pancreatic beta cells enhances insulin secretion.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 217 papers, 1 of them a synthesis that pooled it.
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Who cites it
217 citing papers in PubMed, 1 synthesis or guideline pooled it, 347 citations in OpenAlex.
- Relationships between type 2 diabetes, cell dysfunction, and redox signaling: A meta-analysis of single-cell gene expression of human pancreatic α- and β-cells.Journal of diabetes · 2022Pooled it
- Caloric Restriction Intervention Alters Specific Circulating Biomarkers of the Senescence-Associated Secretome in Middle-Aged and Older Adults With Obesity and Prediabetes in an 18-Week Randomized Controlled Trial.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Trial
- Article
- Epigenetics and childhood obesity: DNA methylation coordinates environment and gene regulation.Endocrine reviews · 2026Review
- Genomic, epigenomic and transcriptomic regulation of cellular senescence.Nature reviews. Genetics · 2026Review
- Aging of hair follicle stem cells and their niche: mechanisms and regenerative therapeutic strategies.Cell communication and signaling : CCS · 2026Review
- β-cell FMO3-produced TMAO prevents NF-κB-mediated senescence and inflammation in ageing and diabetic conditions.Nature communications · 2026Article
- p21-senescent cells drive pancreatic islet dysfunction through targetable paracrine signaling in type 2 diabetes.JCI insight · 2026Article
- Pancreatic β-cell aging in physiology and diabetes: emerging roles of m6A mRNA methylation.Journal of molecular endocrinology · 2026Review
- Advanced drug delivery platforms targeting cellular senescence: A promising strategy for cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- Distinct senescent β-cell senotypes differentially drive islet aging and dysfunction.bioRxiv : the preprint server for biology · 2026Article
- Somatostatin in Aging: Correlations with Selected Central Nervous System and Gastrointestinal Tract Diseases.International journal of molecular sciences · 2026Review
- Review
- Response to Kawamoto et al.EMBO reports · 2026Article
- Development and characterization of experimental β-cell senescence models revealing autophagy defects and altered stimulus-secretion coupling.GeroScience · 2026Article
- Implications of Genetic Elements on Type 2 Diabetes Mellitus Pathogenesis and Management.Endocrinology, diabetes & metabolism · 2026Review
- iCLAP: an innovative method for integrable co-detection of low-abundance antigens with high-plex immunostaining.Nature communications · 2026Article
- Genetic recording of pancreatic beta cell proliferation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Proteomics-derived organ-specific aging clusters predict macrovascular and microvascular complications in diabetes.Cardiovascular diabetology · 2026Article
- DEL-1 is an Endogenous Senolytic Protein that Inhibits Senescence-Associated Bone Loss.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
157 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 5 institutions in 3 countries.
Funding
Abstract
Cellular senescence is thought to contribute to age-associated deterioration of tissue physiology. The senescence effector p16(Ink4a) is expressed in pancreatic beta cells during aging and limits their proliferative potential; however, its effects on beta cell function are poorly characterized. We found that beta cell-specific activation of p16(Ink4a) in transgenic mice enhances glucose-stimulated insulin secretion (GSIS). In mice with diabetes, this leads to improved glucose homeostasis, providing an unexpected functional benefit. Expression of p16(Ink4a) in beta cells induces hallmarks of senescence--including cell enlargement, and greater glucose uptake and mitochondrial activity--which promote increased insulin secretion. GSIS increases during the normal aging of mice and is driven by elevated p16(Ink4a) activity. We found that islets from human adults contain p16(Ink4a)-expressing senescent beta cells and that senescence induced by p16(Ink4a) in a human beta cell line increases insulin secretion in a manner dependent, in part, on the activity of the mechanistic target of rapamycin (mTOR) and the peroxisome proliferator-activated receptor (PPAR)-γ proteins. Our findings reveal a novel role for p16(Ink4a) and cellular senescence in promoting insulin secretion by beta cells and in regulating normal functional tissue maturation with age.
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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.