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Fumarate hydratase deletion in pancreatic beta cells leads to progressive diabetes

Abstract:

We explored the role of the Krebs cycle enzyme fumarate hydratase (FH) in glucose-stimulated insulin secretion (GSIS). Mice lacking Fh1 in pancreatic β cells (Fh1βKO mice) appear normal for 6-8 weeks but then develop progressive glucose intolerance and diabetes. Glucose tolerance is rescued by expression of mitochondrial or cytosolic FH but not by deletion of Hif1α or Nrf2. Progressive hyperglycemia in Fh1βKO mice led to dysregulated metabolism in β cells, a decrease in glucose-induced ATP pr...

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Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1016/j.celrep.2017.08.093

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Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM; Target Discovery Institute
Role:
Author
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Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
RDM; OCDEM
Role:
Author
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Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
RDM; OCDEM
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM; Jenner Institute
Role:
Author
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Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
RDM
Role:
Author
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Funding agency for:
Hamilton, A
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Funding agency for:
Martín-Del-Río, R
Grant:
SAF2009/1267
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Funding agency for:
Rebelato, E
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Publisher:
Elsevier Publisher's website
Journal:
Cell Reports Journal website
Volume:
20
Issue:
13
Pages:
3135-3148
Publication date:
2017-09-26
Acceptance date:
2017-08-29
DOI:
EISSN:
2211-1247
ISSN:
2211-1247
Pmid:
28954230
Source identifiers:
731155
Language:
English
Keywords:
Pubs id:
pubs:731155
UUID:
uuid:d592f689-b891-493b-ac78-7070faa19ae8
Local pid:
pubs:731155
Deposit date:
2017-10-14

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