Aldolase-regulated G3BP1/2+ condensates control insulin mRNA storage in beta cells

ABSTRACT: Upregulation of insulin mRNA translation upon hyperglycemia in pancreatic islet ꞵ-cells involves several RNA-binding proteins. Here, we found that G3BP1, a stress granule marker downregulated in islets of subjects with type 2 diabetes, binds to insulin mRNA in glucose concentration-dependent manner. We show in mouse insulinoma MIN6-K8 cells exposed to fasting glucose levels that G3BP1 and its paralog G3BP2 colocalize to cytosolic condensates with eIF3b, phospho-AMPKαThr172 and Ins1/2 mRNA. Glucose stimulation dissolves G3BP1+/2+ condensates with cytosolic redistribution of their components. The aldolase inhibitor aldometanib prevents the glucose- and pyruvate-induced dissolution of G3BP1+/2+ condensates, increases phospho-AMPKαThr172 levels and reduces those of phospho-mTORSer2448. G3BP1 o

SUBMITTER: Esteban Quezada 

PROVIDER: S-SCDT-10_1038-S44318-025-00448-7 | biostudies-other |

REPOSITORIES: biostudies-other