English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  The FOXP1, FOXP2 and FOXP4 transcription factors are required for islet alpha cell proliferation and function in mice

Spaeth, J. M., Hunter, C. S., Bonatakis, L., Guo, M., French, C. A., Slack, I., et al. (2015). The FOXP1, FOXP2 and FOXP4 transcription factors are required for islet alpha cell proliferation and function in mice. Diabetologia, 58, 1836-1844. doi:10.1007/s00125-015-3635-3.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-9D94-C Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-2A8D-4
Genre: Journal Article

Files

show Files
hide Files
:
125_2015_3635_MOESM1_ESM.pdf (Supplementary material), 598KB
Name:
125_2015_3635_MOESM1_ESM.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
125_2015_3635_MOESM2_ESM.pdf (Supplementary material), 637KB
Name:
125_2015_3635_MOESM2_ESM.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
125_2015_3635_MOESM3_ESM.pdf (Supplementary material), 740KB
Name:
125_2015_3635_MOESM3_ESM.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
125_2015_3635_MOESM4_ESM.pdf (Supplementary material), 896KB
Name:
125_2015_3635_MOESM4_ESM.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
125_2015_3635_MOESM5_ESM.pdf (Supplementary material), 698KB
Name:
125_2015_3635_MOESM5_ESM.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
125_2015_3635_MOESM6_ESM.pdf (Supplementary material), 474KB
Name:
125_2015_3635_MOESM6_ESM.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
125_2015_3635_MOESM7_ESM.pdf (Supplementary material), 759KB
Name:
125_2015_3635_MOESM7_ESM.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
125_2015_3635_MOESM8_ESM-1.pdf (Supplementary material), 791KB
Name:
125_2015_3635_MOESM8_ESM-1.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
Spaeth_etal_diabetologia_2015.pdf (Publisher version), 5MB
Name:
Spaeth_etal_diabetologia_2015.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
Spaeth, Jason M.1, Author
Hunter, Chad S.1, 2, Author
Bonatakis, Lauren1, Author
Guo, Min1, Author
French, Catherine A.3, Author
Slack, Ian4, Author
Hara, Manami5, Author
Fisher, Simon E.6, 7, Author              
Ferrer, Jorge8, Author
Morrisey, Edward E.4, Author
Stanger, Ben Z.4, Author
Stein, Roland1, Author
Affiliations:
1Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN, USA, ou_persistent22              
2Department of Medicine, Division of Endocrinology Diabetes & Metabolism, University of Alabama at Birmingham, Birmingham, AL, USA, ou_persistent22              
3Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, Lisbon, Portugal, ou_persistent22              
4Department of Medicine and Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA, USA, ou_persistent22              
5Department of Medicine, University of Chicago, Chicago, IL, USA, ou_persistent22              
6Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society, ou_792549              
7Donders Institute for Brain, Cognition and Behaviour, External Organizations, ou_55236              
8Department of Medicine, Imperial Centre for Translational and Experimental Medicine, Imperial College London, London, UK, ou_persistent22              

Content

show
hide
Free keywords: -
 Abstract: Aims/hypothesis Several forkhead box (FOX) transcription factor family members have important roles in controlling pancreatic cell fates and maintaining beta cell mass and function, including FOXA1, FOXA2 and FOXM1. In this study we have examined the importance of FOXP1, FOXP2 and FOXP4 of the FOXP subfamily in islet cell development and function. Methods Mice harbouring floxed alleles for Foxp1, Foxp2 and Foxp4 were crossed with pan-endocrine Pax6-Cre transgenic mice to generate single and compound Foxp mutant mice. Mice were monitored for changes in glucose tolerance by IPGTT, serum insulin and glucagon levels by radioimmunoassay, and endocrine cell development and proliferation by immunohistochemistry. Gene expression and glucose-stimulated hormone secretion experiments were performed with isolated islets. Results Only the triple-compound Foxp1/2/4 conditional knockout (cKO) mutant had an overt islet phenotype, manifested physiologically by hypoglycaemia and hypoglucagonaemia. This resulted from the reduction in glucagon-secreting alpha cell mass and function. The proliferation of alpha cells was profoundly reduced in Foxp1/2/4 cKO islets through the effects on mediators of replication (i.e. decreased Ccna2, Ccnb1 and Ccnd2 activators, and increased Cdkn1a inhibitor). Adult islet Foxp1/2/4 cKO beta cells secrete insulin normally while the remaining alpha cells have impaired glucagon secretion. Conclusions/interpretation Collectively, these findings reveal an important role for the FOXP1, 2, and 4 proteins in governing postnatal alpha cell expansion and function.

Details

show
hide
Language(s): eng - English
 Dates: 20152015
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1007/s00125-015-3635-3
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Diabetologia
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Heidelberg : Springer-Verlag Heidelberg
Pages: - Volume / Issue: 58 Sequence Number: - Start / End Page: 1836 - 1844 Identifier: ISSN: 0012-186X
CoNE: https://pure.mpg.de/cone/journals/resource/954925394387