ArticleThe Journal of clinical investigation2009
The insulin/Akt pathway controls a specific cell division program that leads to generation of binucleated tetraploid liver cells in rodents.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 144 citations in OpenAlex.
- Generation of tetraploid organs in mice.Zoological research · 2026Article
- Stereo-cell deciphers the spatial and functional heterogeneity of polyploid hepatocytes.GigaScience · 2026Article
- Loss of endothelial ZEB2 in mice attenuates steatosis early during metabolic dysfunction-associated steatotic liver disease.Scientific reports · 2025Article
- Breaking the rules of cell biology: Lessons from the liver's exceptional regenerative capacity.Molecular biology of the cell · 2025Review
- Macrophage-Derived Type 1 IFN, Renal Tubular Epithelial Cell Polyploidization, and AKI-to-CKD Transition.Journal of the American Society of Nephrology : JASN · 2025Article
- Paracancerous binuclear hepatocytes assessed by computer program is a novel biomarker for short term recurrence of hepatocellular carcinoma after surgery.Scientific reports · 2025Article
- ESRP2-microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation.Genes & development · 2025Article
- Article
- Review
- Binucleated human hepatocytes arise through late cytokinetic regression during endomitosis M phase.The Journal of cell biology · 2024Article
- The Ploidy State as a Determinant of Hepatocyte Proliferation.Seminars in liver disease · 2023Review
- Conserved chamber-specific polyploidy maintains heart function in Drosophila.Development (Cambridge, England) · 2023Article
- Cellular polyploidy in organ homeostasis and regeneration.Protein & cell · 2023Article
- Distinct hepatocyte identities in liver homeostasis and regeneration.JHEP reports : innovation in hepatology · 2023Review
- Regulation of Cellular Senescence in Type 2 Diabetes Mellitus: From Mechanisms to Clinical Applications.Diabetes & metabolism journal · 2023Review
- Review
- Inhibition of polyploidization in Pten-deficient livers reduces steatosis.Liver international : official journal of the International Association for the Study of the Liver · 2022Article
- Tubular cell polyploidy protects from lethal acute kidney injury but promotes consequent chronic kidney disease.Nature communications · 2022Article
- Implications of Polyploidy and Ploidy Alterations in Hepatocytes in Liver Injuries and Cancers.International journal of molecular sciences · 2022Review
- Centriole signaling restricts hepatocyte ploidy to maintain liver integrity.Genes & development · 2022Article
28 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
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The formation of polyploid cells is part of the developmental program of several tissues. During postnatal development, binucleated tetraploid cells arise in the liver, caused by failure in cytokinesis. In this report, we have shown that the initiation of cytokinesis failure events and the subsequent appearance of binucleated tetraploid cells are strictly controlled by the suckling-to-weaning transition in rodents. We found that daily light/dark rhythms and carbohydrate intake did not affect liver tetraploidy. In contrast, impairment of insulin signaling drastically reduced the formation of binucleated tetraploid cells, whereas repeated insulin injections promoted the generation of these liver cells. Furthermore, inhibition of Akt activity decreased the number of cytokinesis failure events, possibly through the mammalian target of rapamycin signaling complex 2 (mTORC2), which indicates that the PI3K/Akt pathway lies downstream of the insulin signal to regulate the tetraploidization process. To our knowledge, these results are the first demonstration in a physiological context that insulin signaling through Akt controls a specific cell division program and leads to the physiologic generation of binucleated tetraploid liver cells.
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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.