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Genetic protection from type 1 diabetes resulting from accelerated insulin mRNA decay.

Cell - 1 May 2025

van Tienhoven René, O'Meally Denis, Scott Tristan A, Morris Kevin V, Williams John C, Kaddis John S, Zaldumbide Arnaud, Roep Bart O

Abstract excerpt

Insulin gene (INS) variation and beta-cell stress are associated with the risk of development of type 1 diabetes (T1D) and autoimmunity against insulin. The unfolded protein response alleviating endoplasmic reticulum (ER) stress involves activation of inositol-requiring enzyme 1α (IRE1α) that impedes translation by mRNA decay. We discover that the IRE1α digestion motif is present in insulin mRNA carrying SNP...

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PMID: 40112799
DOI: 10.1016/j.cell.2025.02.018

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INS

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