A Selective Cullin 3 RING E3 Ligase Inhibitor Attenuates Hyperglycemia via Dual Insulin Sensitizing and Insulinotropic Action.

Gu, Lijie; Xiong, Lei; Hasan, Mohammad Nazmul; Du, Yanhong; Wu, Timothy; Li, Tiangang · Diabetes · 2026

basic_science · Level V

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Abstract

Pan-neddylation inhibitors exhibit potent hypoglycemic effect. The target organs and mechanisms underlying the hypoglycemia effect of pan-neddylation inhibitors are incompletely understood. We found that inhibition of cullin 3 leads to a dual insulin sensitization and insulinotropic effect. Selective inhibition of cullin 3 neddylation is a feasible approach to lower hyperglycemia.