EIF4G1 and carboxypeptidase E axis dysregulation in O-GlcNAc transferase-deficient pancreatic β-cells contributes to hyperproinsulinemia in mice.

ABSTRACT: An early hallmark of type 2 diabetes is a failure of proinsulin-to-insulin processing in pancreatic β-cells, resulting in hyperproinsulinemia. Proinsulin processing is quite sensitive to nutrient flux, and β-cell-specific deletion of the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO) causes β-cell failure and diabetes, including early development of hyperproinsulinemia. The mechanisms underlying this latter defect are unknown. Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin proces

SUBMITTER: Jo S 

PROVIDER: S-EPMC6721936 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature