AI Article Synopsis
- * Coding variants in PAM are linked to increased T2D risk and affect insulin production and secretion.
- * Findings show that PAM deficiency leads to lower insulin levels and dysfunctional insulin secretion, highlighting its importance in β-cell function and clarifying how specific genetic variants contribute to T2D risk.
Article Abstract
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 primary islets from cadaveric donors. Thus, our results demonstrate a role for PAM in β-cell function, and establish molecular mechanisms for T2D risk alleles at this locus.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237273 | PMC |
| http://dx.doi.org/10.1038/s41588-018-0173-1 | DOI Listing |
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