Ectopic expression of E2F1 stimulates beta cell proliferation and function

Item Type:	Article
Title:	Ectopic expression of E2F1 stimulates beta cell proliferation and function
Creators Name:	Grouwels, G. and Cai, Y. and Hoebeke, I. and Leuckx, G. and Heremans, Y. and Ziebold, U. and Stange, G. and Chintinne, M. and Ling, Z. and Pipeleers, D. and Heimberg, H. and Van de Casteele, M.
Abstract:	Objective - Generating functional beta cells by inducing their proliferation might open perspectives for cell therapy in diabetes. Transcription factor E2F1 controls G1- to S-phase transition during the cycling of many cell types and is required for pancreatic beta cell growth and function. However, the consequences of overexpression of E2F1 in beta cells are unknown. Research design and methods - The effects of E2F1 overexpression on beta cell proliferation and function were analyzed in isolated rat beta cells and in transgenic mice. Results - Adenovirus AdE2F1-mediated overexpression of E2F1 increased the proliferation of isolated primary rat beta cells 20-fold but also enhanced beta cell death. Co-infection with adenovirus AdAkt expressing a constitutively active form of Akt (protein kinase B) suppressed beta cell death to control levels. At 48h post-infection, the total beta cell number and insulin content were respectively 46% and 79% higher in AdE2F1+AdAkt-infected cultures as compared to untreated. Conditional overexpression of E2F1 in mice resulted in a 2-fold increase of beta cell proliferation and 70% increase of pancreatic insulin content, but did not increase beta cell mass. Glucose-challenged insulin release was increased, and the mice showed protection against toxin-induced diabetes. Conclusions - Overexpression of E2F1, either in vitro or in vivo, can stimulate beta cell proliferation activity. In vivo E2F1 expression significantly increases the insulin content and function of adult beta cells, making it a strategic target for therapeutic manipulation of beta cell function.
Keywords:	Arrhythmogenic Right Ventricular Dysplasia, Cardiac Sudden Death, Cell Cycle, Cell Death, Cell Division, Desmosomes, Differential Diagnosis, Disease Progression, E2F1 Transcription Factor, Gene Expression Regulation, Heart Ventricles, Immunohistochemistry, Insulin-Secreting Cells, Mutation, Pancreas, Risk Factors, Animals, Mice, Rats
Source:	Diabetes
ISSN:	0012-1797
Publisher:	American Diabetes Association
Volume:	59
Number:	6
Page Range:	1435-1444
Date:	June 2010
Official Publication:	https://doi.org/10.2337/db09-1295
PubMed:	View item in PubMed

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