Inhibition of hepatic glycogen synthesis by hyperhomocysteinemia mediated by TRB3.

ABSTRACT: Recently, epidemiological and experimental studies have linked hyperhomocysteinemia (HHcy) to insulin resistance. However, whether HHcy impairs glucose homeostasis by affecting glycogenesis in the liver is not clear. In the present study, we investigated the effect of HHcy on hepatic glycogen synthesis. Hyperhomocysteinemia was induced in mice by drinking water containing two percent methionine. Mice with HHcy showed an increase in the phosphorylation of glycogen synthase and a significant decrease in hepatic glycogen content and the rate of glycogen synthesis. The expression of TRB3 (tribbles-related protein 3) was up-regulated in the liver of mice with HHcy, concomitantly with the dephosphorylation of glycogen synthase kinase-3β and Akt. The knockdown of TRB3 by short hairpin RNA suppres

SUBMITTER: Liu WJ 

PROVIDER: S-EPMC3078444 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature