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Journal article

Type 2 diabetes risk alleles in PAM impact insulin release from human pancreatic beta cells

Abstract:

The molecular mechanisms underpinning GWAS loci for type 2 diabetes (T2D) remain poorly understood. Coding variants in peptidylglycine alpha-amidating monooxygenase (PAM) are associated with both T2D risk and insulinogenic index. Here, we demonstrate that the T2D risk alleles impact negatively on overall PAM activity, via defects in expression and catalytic function. PAM deficiency results in reduced insulin content and altered dynamics of insulin secretion in a human beta cell model and prim...

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Publication status:
Published
Peer review status:
Peer reviewed
Version:
Accepted manuscipt

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Publisher copy:
10.1038/s41588-018-0173-1

Authors


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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:
RDM; OCDEM
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
Biochemistry
Role:
Author
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Radcliffe Department of Medicine More from this funder
Horizon 2020 More from this funder
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Publisher:
Nature Publishing Group Publisher's website
Journal:
Nature Genetics Journal website
Volume:
50
Issue:
7
Pages:
1122–1131
Publication date:
2018-07-27
Acceptance date:
2018-06-06
DOI:
EISSN:
1546-1718
ISSN:
1061-4036
Pubs id:
pubs:856551
URN:
uri:6d0e0ce6-6b37-4969-a1d2-118e64b215c3
UUID:
uuid:6d0e0ce6-6b37-4969-a1d2-118e64b215c3
Local pid:
pubs:856551

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