4-Aminoethylamino-emodin--a novel potent inhibitor of GSK-3beta--acts as an insulin-sensitizer avoiding downstream effects of activated beta-catenin.

ABSTRACT: Glycogen synthase kinase-3beta (GSK-3beta) is a key target and effector of downstream insulin signalling. Using comparative protein kinase assays and molecular docking studies we characterize the emodin-derivative 4-[N-2-(aminoethyl)-amino]-emodin (L4) as a sensitive and potent inhibitor of GSK-3beta with peculiar features. Compound L4 shows a low cytotoxic potential compared to other GSK-3beta inhibitors determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay and cellular ATP levels. Physiologically, L4 acts as an insulin-sensitizing agent that is able to enhance hepatocellular glycogen and fatty acid biosynthesis. These functions are particularly stimulated in the presence of elevated concentrations of glucose and in synergy with the hormone action at modera

SUBMITTER: Gebhardt R 

PROVIDER: S-EPMC3828845 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature