HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Online-Only Appendix All Versions of this Article: db08-0878v1 57/11/3069    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Ackermann Misfeldt, A. Articles by Gannon, M. PubMed PubMed Citation Articles by Ackermann Misfeldt, A. Articles by Gannon, M. Social Bookmarking                What's this?

β-Cell Proliferation, but not Neogenesis, Following 60% Partial Pancreatectomy is Impaired in the Absence of FoxM1

¹Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, Tennessee
²Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee
³Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee
⁴Program in Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee
⁵Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois

Objective: This study was designed to determine whether the transcription factor FoxM1 was required for regeneration of β-cell mass via proliferation and/or neogenesis in the adult after 60% partial pancreatectomy (PPx).

Research Design and Methods: Adult mice with a pancreas-wide deletion of Foxm1 (Foxm1^flox/flox;Pdx1-Cre [FoxM1^panc]) and their Control littermates (Foxm1^flox/flox) were subjected to PPx or a Sham operation, after which islet expression of Foxm1 and several target genes, β-cell mass, proliferation, β-cell size, islet size, islet density, and Neurogenin3 expression were analyzed.

Results: In Control mice, PPx stimulated β-cell proliferation and neogenesis and up-regulated Foxm1 and several of its known targets (Plk1, Cenp-a, Birc5/Survivin, Ccnb1) in islets. Within 1 week post-PPx, Control mice underwent significant regeneration of β-cell mass, and average islet size within the regenerating lobe was similar to that after a sham operation. However, FoxM1^panc mice exhibited specific impairments in β-cell mass regeneration and islet growth after PPx, with reduced proliferation of and β-cells but no impairments in acinar or ductal cell proliferation. Interestingly, FoxM1 was not required for proliferation of β-cells within small endocrine cell clusters located in the regenerating portion of the pancreas, but was specifically required for proliferation of β-cells within larger islets. Additionally, FoxM1 was not required for β-cell neogenesis following PPx.

Conclusions: Our results indicate that FoxM1 is partially required for increased β-cell proliferation, but not β-cell neogenesis, stimulated by PPx. Furthermore, FoxM1 seems to be dispensable for proliferation of β-cells following neogenesis but is required for proliferation of pre-existing β-cells.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?