Type 2 diabetes risk alleles in PAM impact insulin release from human pancreatic ?-cells.
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ABSTRACT:
SUBMITTER: Thomsen SK
PROVIDER: S-EPMC6237273 | biostudies-literature | 2018 Aug
REPOSITORIES: biostudies-literature
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Type 2 diabetes risk alleles in PAM impact insulin release from human pancreatic β-cells.
Thomsen Soren K SK Raimondo Anne A Hastoy Benoit B Sengupta Shahana S Dai Xiao-Qing XQ Bautista Austin A Censin Jenny J Payne Anthony J AJ Umapathysivam Mahesh M MM Spigelman Aliya F AF Barrett Amy A Groves Christopher J CJ Beer Nicola L NL Manning Fox Jocelyn E JE McCarthy Mark I MI Clark Anne A Mahajan Anubha A Rorsman Patrik P MacDonald Patrick E PE Gloyn Anna L AL
Nature genetics 20180727 8
The molecular mechanisms underpinning susceptibility loci for type 2 diabetes (T2D) remain poorly understood. Coding variants in peptidylglycine α-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 β-cell model and prima ...[more]
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