OSGEP regulates islet β-cell function by modulating proinsulin translation and maintaining ER stress homeostasis in mice.

ABSTRACT: Proinsulin translation and folding is crucial for glucose homeostasis. However, islet β-cell control of Proinsulin translation remains incompletely understood. Here, we identify OSGEP, an enzyme responsible for t⁶A₃₇ modification of tRNA^NNU that tunes glucose metabolism in β-cells. Global Osgep deletion causes glucose intolerance, while β-cell-specific deletion induces hyperglycemia and glucose intolerance due to impaired insulin activity. Transcriptomics and proteomics reveal activation of the unfolded protein response (UPR) and apoptosis signaling pathways in Osgep-deficient islets, linked to an increase in misfolded Proinsulin from reduced t⁶A₃₇ modification. Osgep overexpression in pancreas rescues insulin secretion and mitigates d

SUBMITTER: Liu Y 

PROVIDER: S-EPMC11612026 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature