A selective Cullin 3 RING E3 ligase inhibitor attenuates hyperglycemia via dual insulin sensitizing and insulinotropic action

a. Pan cullin neddylation inhibitors exhibit potent hypoglycemic effect.b. The target organs and mechanisms underlying the hypoglycemia effect of cullin pan neddylation inhibitors are incompletely understood.c. We found that inhibition of Cul3 leads to a dual insulin sensitization and insulinotropic effect.d. Selective inhibition of Cul3 neddylation is a feasible approach to lower hyperglycemia.