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Ectopic expression of E2F1 stimulates beta-Cell proliferation and function

Gael Grouwels, Ying Cai, Inge Hoebeke UGent, Gunter Leuckx, Yves Heremans, Ulrike Ziebold, Geert Stange, Marie Chintinne, Zhidong Ling, Daniel Pipeleers, et al. (2010) DIABETES. 59(6). p.1435-1444
abstract
OBJECTIVE-Generating functional beta-cells by inducing their proliferation may provide new perspectives for cell therapy in diabetes. Transcription factor E2F1 controls G(1)- 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. Coinfection with adenovirus Ad Akt expressing a constitutively active form of Akt (protein kinase B) suppressed beta-cell death to control levels. At 48 h after infection, the total beta-cell number and insulin content were, respectively, 46 and 79% higher in AdE2F1+AdAkt-infected cultures compared with untreated. Conditional overexpression of E2F1 in mice resulted in a twofold increase of beta-cell proliferation and a 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. Diabetes 59:1435-1444, 2010
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
GROWTH, MASS, PROTEIN, DIFFERENTIATION, APOPTOSIS, HUMAN PANCREATIC-DUCT, KINASE-B, MUTANT MICE, TRANSCRIPTION FACTOR, ADULT-MOUSE PANCREAS
journal title
DIABETES
Diabetes
volume
59
issue
6
pages
1435 - 1444
Web of Science type
Article
Web of Science id
000278844700017
JCR category
ENDOCRINOLOGY & METABOLISM
JCR impact factor
8.889 (2010)
JCR rank
5/115 (2010)
JCR quartile
1 (2010)
ISSN
0012-1797
DOI
10.2337/db09-1295
language
English
UGent publication?
no
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1235510
handle
http://hdl.handle.net/1854/LU-1235510
date created
2011-05-25 09:21:59
date last changed
2016-12-19 15:39:51
@article{1235510,
  abstract     = {OBJECTIVE-Generating functional beta-cells by inducing their proliferation may provide new perspectives for cell therapy in diabetes. Transcription factor E2F1 controls G(1)- 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. Coinfection with adenovirus Ad Akt expressing a constitutively active form of Akt (protein kinase B) suppressed beta-cell death to control levels. At 48 h after infection, the total beta-cell number and insulin content were, respectively, 46 and 79\% higher in AdE2F1+AdAkt-infected cultures compared with untreated. Conditional overexpression of E2F1 in mice resulted in a twofold increase of beta-cell proliferation and a 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. Diabetes 59:1435-1444, 2010},
  author       = {Grouwels, Gael and Cai, Ying and Hoebeke, Inge and Leuckx, Gunter and Heremans, Yves and Ziebold, Ulrike and Stange, Geert and Chintinne, Marie and Ling, Zhidong and Pipeleers, Daniel and Heimberg, Harry and Van de Casteele, Mark},
  issn         = {0012-1797},
  journal      = {DIABETES},
  keyword      = {GROWTH,MASS,PROTEIN,DIFFERENTIATION,APOPTOSIS,HUMAN PANCREATIC-DUCT,KINASE-B,MUTANT MICE,TRANSCRIPTION FACTOR,ADULT-MOUSE PANCREAS},
  language     = {eng},
  number       = {6},
  pages        = {1435--1444},
  title        = {Ectopic expression of E2F1 stimulates beta-Cell proliferation and function},
  url          = {http://dx.doi.org/10.2337/db09-1295},
  volume       = {59},
  year         = {2010},
}

Chicago
Grouwels, Gael, Ying Cai, Inge Hoebeke, Gunter Leuckx, Yves Heremans, Ulrike Ziebold, Geert Stange, et al. 2010. “Ectopic Expression of E2F1 Stimulates beta-Cell Proliferation and Function.” Diabetes 59 (6): 1435–1444.
APA
Grouwels, G., Cai, Y., Hoebeke, I., Leuckx, G., Heremans, Y., Ziebold, U., Stange, G., et al. (2010). Ectopic expression of E2F1 stimulates beta-Cell proliferation and function. DIABETES, 59(6), 1435–1444.
Vancouver
1.
Grouwels G, Cai Y, Hoebeke I, Leuckx G, Heremans Y, Ziebold U, et al. Ectopic expression of E2F1 stimulates beta-Cell proliferation and function. DIABETES. 2010;59(6):1435–44.
MLA
Grouwels, Gael, Ying Cai, Inge Hoebeke, et al. “Ectopic Expression of E2F1 Stimulates beta-Cell Proliferation and Function.” DIABETES 59.6 (2010): 1435–1444. Print.