Ectopic expression of E2F1 stimulates β-cell proliferation and function

24Citations
Citations of this article
37Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

OBJECTIVE - Generating functional β-cells by inducing their proliferation may provide new 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 β-cell growth and function. However, the consequences of overexpression of E2F1 in β-cells are unknown. RESEARCH DESIGN AND METHODS - The effects of E2F1 overexpression on β-cell proliferation and function were analyzed in isolated rat β-cells and in transgenic mice. RESULTS - Adenovirus AdE2F1-mediated overexpression of E2F1 increased the proliferation of isolated primary rat β-cells 20-fold but also enhanced β-cell death. Coinfection with adenovirus AdAkt expressing a constitutively active form of Akt (protein kinase B) suppressed β-cell death to control levels. At 48 h after infection, the total β-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 β-cell proliferation and a 70% increase of pancreatic insulin content, but did not increase β-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 β-cell proliferation activity. In vivo E2F1 expression significantly increases the insulin content and function of adult β-cells, making it a strategic target for therapeutic manipulation of β-cell function. © 2010 by the American Diabetes Association.

Cite

CITATION STYLE

APA

Grouwels, G., Cai, Y., Hoebeke, I., Leuckx, G., Heremans, Y., Ziebold, U., … Van De Casteele, M. (2010). Ectopic expression of E2F1 stimulates β-cell proliferation and function. Diabetes, 59(6), 1435–1444. https://doi.org/10.2337/db09-1295

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free