The insulin/Akt pathway controls a specific cell division program that leads to generation of binucleated tetraploid liver cells in rodents
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 subsequen...
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Veröffentlicht in: | The Journal of clinical investigation 2009-07, Vol.119 (7), p.1880-1887 |
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creator | Celton-Morizur, Séverine Merlen, Grégory Couton, Dominique Margall-Ducos, Germain Desdouets, Chantal |
description | 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. |
doi_str_mv | 10.1172/jci38677 |
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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.</description><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/jci38677</identifier><identifier>PMID: 19603546</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>Animals ; Biomedical research ; Carbohydrates ; Cell cycle ; Cell Division ; Cellular signal transduction ; Dietary Carbohydrates - administration & dosage ; Hepatocytes - physiology ; Human health and pathology ; Hépatology and Gastroenterology ; Insulin ; Insulin - physiology ; Life Sciences ; Liver ; Liver cells ; Mice ; Mice, Obese ; Phosphatidylinositol 3-Kinases - physiology ; Physiological aspects ; Physiology ; Polyploidy ; Proto-Oncogene Proteins c-akt - physiology ; Rats ; Rats, Wistar ; Rodents ; Signal Transduction ; Smooth muscle ; Weaning</subject><ispartof>The Journal of clinical investigation, 2009-07, Vol.119 (7), p.1880-1887</ispartof><rights>COPYRIGHT 2009 American Society for Clinical Investigation</rights><rights>Copyright American Society for Clinical Investigation Jul 2009</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Copyright © 2009, American Society for Clinical Investigation</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c649t-91fdd5d29a2b6cba0b1ad9aea0df3d4c692b24df0293c1ef4901e2b2c19030873</citedby><cites>FETCH-LOGICAL-c649t-91fdd5d29a2b6cba0b1ad9aea0df3d4c692b24df0293c1ef4901e2b2c19030873</cites><orcidid>0000-0001-5622-9777</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701880/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701880/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19603546$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://inserm.hal.science/inserm-00404399$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Celton-Morizur, Séverine</creatorcontrib><creatorcontrib>Merlen, Grégory</creatorcontrib><creatorcontrib>Couton, Dominique</creatorcontrib><creatorcontrib>Margall-Ducos, Germain</creatorcontrib><creatorcontrib>Desdouets, Chantal</creatorcontrib><title>The insulin/Akt pathway controls a specific cell division program that leads to generation of binucleated tetraploid liver cells in rodents</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>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.</description><subject>Animals</subject><subject>Biomedical research</subject><subject>Carbohydrates</subject><subject>Cell cycle</subject><subject>Cell Division</subject><subject>Cellular signal transduction</subject><subject>Dietary Carbohydrates - administration & dosage</subject><subject>Hepatocytes - physiology</subject><subject>Human health and pathology</subject><subject>Hépatology and Gastroenterology</subject><subject>Insulin</subject><subject>Insulin - physiology</subject><subject>Life Sciences</subject><subject>Liver</subject><subject>Liver cells</subject><subject>Mice</subject><subject>Mice, Obese</subject><subject>Phosphatidylinositol 3-Kinases - physiology</subject><subject>Physiological aspects</subject><subject>Physiology</subject><subject>Polyploidy</subject><subject>Proto-Oncogene Proteins c-akt - 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administration & dosage</topic><topic>Hepatocytes - physiology</topic><topic>Human health and pathology</topic><topic>Hépatology and Gastroenterology</topic><topic>Insulin</topic><topic>Insulin - physiology</topic><topic>Life Sciences</topic><topic>Liver</topic><topic>Liver cells</topic><topic>Mice</topic><topic>Mice, Obese</topic><topic>Phosphatidylinositol 3-Kinases - physiology</topic><topic>Physiological aspects</topic><topic>Physiology</topic><topic>Polyploidy</topic><topic>Proto-Oncogene Proteins c-akt - physiology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Rodents</topic><topic>Signal Transduction</topic><topic>Smooth muscle</topic><topic>Weaning</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Celton-Morizur, Séverine</creatorcontrib><creatorcontrib>Merlen, Grégory</creatorcontrib><creatorcontrib>Couton, Dominique</creatorcontrib><creatorcontrib>Margall-Ducos, Germain</creatorcontrib><creatorcontrib>Desdouets, Chantal</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints in Context (Gale)</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>SIRS Editorial</collection><collection>MEDLINE - 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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.</abstract><cop>United States</cop><pub>American Society for Clinical Investigation</pub><pmid>19603546</pmid><doi>10.1172/jci38677</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-5622-9777</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animals Biomedical research Carbohydrates Cell cycle Cell Division Cellular signal transduction Dietary Carbohydrates - administration & dosage Hepatocytes - physiology Human health and pathology Hépatology and Gastroenterology Insulin Insulin - physiology Life Sciences Liver Liver cells Mice Mice, Obese Phosphatidylinositol 3-Kinases - physiology Physiological aspects Physiology Polyploidy Proto-Oncogene Proteins c-akt - physiology Rats Rats, Wistar Rodents Signal Transduction Smooth muscle Weaning |
title | The insulin/Akt pathway controls a specific cell division program that leads to generation of binucleated tetraploid liver cells in rodents |
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