CDK4, pRB and E2F1: connected to insulin. - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Cell Division Année : 2010

CDK4, pRB and E2F1: connected to insulin.

Résumé

Pancreatic beta-cells are metabolic sensors involved in the control of glucose homeostasis. This particular cell type controls insulin secretion through a fine-tuned process, which dregulation have important pathological consequences, such as observed during type 2 diabetes. We recently implicated E2F1 in the control of glucose homeostasis. First we showed that E2f1-/- mice have decreased pancreatic size, as the result of impaired postnatal pancreatic growth. We observed in this study that E2F1 was highly expressed in non-proliferating pancreatic beta-cells, suggesting that E2F1, besides the control of beta-cell number could have a role in pancreatic beta-cell function. We demonstrate in our recent study, both in vitro and in vivo that E2F1 directly regulates the expression of Kir6.2, a key component of the KATP channel involved in the regulation of glucose-induced insulin secretion in pancreatic beta-cells. Expression of Kir6.2 is lost in pancreas of E2f1-/- mice, resulting in insulin secretion defects in these mice. Furthermore, we demonstrated by in tissue chromatin immunoprecipitation analysis that regulation of Kir6.2 expression by E2F1 follows the same regulatory pathway that the classical E2F1 target genes, implicating the participation of CDK4 and retinoblastoma protein. Moreover, in this context, E2F1 transcriptional activity is regulated by glucose and insulin through the CDK4-dependent inactivation of the pRB protein. In summary we provide evidence that the CDK4-pRB-E2F1 regulatory pathway is involved in glucose homeostasis. In our recent study we decipher a new function for these factors in the control of insulin secretion and open up new avenues for the treatment of metabolic diseases, in particular type 2 diabetes.
Fichier principal
Vignette du fichier
1747-1028-5-6.pdf (185.18 Ko) Télécharger le fichier
1747-1028-5-6.xml (42.24 Ko) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Format : Autre
Loading...

Dates et versions

inserm-00663531 , version 1 (27-01-2012)

Identifiants

Citer

Lluis Fajas, Emilie Blanchet, Jean-Sébastien Annicotte. CDK4, pRB and E2F1: connected to insulin.. Cell Division, 2010, 5 (1), pp.6. ⟨10.1186/1747-1028-5-6⟩. ⟨inserm-00663531⟩
267 Consultations
186 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More