The insulin/Akt pathway controls a specific cell division program that leads to generation of binucleated tetraploid liver cells in rodents. - Archive ouverte HAL Access content directly
Journal Articles Journal of Clinical Investigation Year : 2009

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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Séverine Celton-Morizur
Grégory Merlen
  • Function : Author
  • PersonId : 861951
Dominique Couton
  • Function : Author
  • PersonId : 861952
Germain Margall-Ducos
  • Function : Author
  • PersonId : 861953
Chantal Desdouets
  • Function : Correspondent author
  • PersonId : 861954

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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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Dates and versions

inserm-00404399 , version 1 (16-07-2009)

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  • HAL Id : inserm-00404399 , version 1
  • PUBMED : 19603546

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Séverine Celton-Morizur, Grégory Merlen, Dominique Couton, Germain Margall-Ducos, Chantal Desdouets. The insulin/Akt pathway controls a specific cell division program that leads to generation of binucleated tetraploid liver cells in rodents.. Journal of Clinical Investigation, 2009, 119 (7), pp.1880-1887. ⟨inserm-00404399⟩
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