Received for publication October 20, 2006.
Revised January 2, 2007.
Accepted for publication January 2, 2007.

Conjugated bile acids regulate hepatocyte glycogen synthase activity in vitro and in vivo via G_i signaling

Abstract

The regulation of glycogen synthase activity by bile acids in primary hepatocytes and in the intact liver was investigated. Bile acids (deoxycholic acid, DCA; taurocholic acid, TCA) activated AKT and glycogen synthase (GS) in primary rat hepatocytes. Incubation with a PI3K inhibitor or expression of dominant negative AKT in primary rat hepatocytes abolished activation of AKT and GS by DCA and TCA. TCA, but not DCA, activated G_i proteins in primary rat hepatocytes. Treatment of cells with pertussis toxin or expression of dominant negative G_i blocked TCA-induced activation of AKT and of GS, but did not alter AKT or GS activation caused by DCA. TCA caused activation of AKT and GS in intact rat liver. Expression of dominant negative G_i reduced TCA-induced activation of AKT and of GS in intact rat liver. Collectively, our findings demonstrate that bile acids are physiologic regulators of glycogen synthase in rat liver and that conjugated bile acids utilize a G_i-coupled GPCR to regulate GS activity in vitro and in vivo.

Key words: Orphan, Insulin, Gi family, Protein Kinases (other), G protein regulation