PT  - JOURNAL ARTICLE
AU  - Youwen Fang
AU  - Elaine Studer
AU  - Clint Mitchell
AU  - Steven Grant
AU  - William M. Pandak
AU  - Philip B. Hylemon
AU  - Paul Dent
TI  - Conjugated Bile Acids Regulate Hepatocyte Glycogen Synthase Activity In Vitro and In Vivo via Gα<sub>i</sub> Signaling
AID  - 10.1124/mol.106.032060
DP  - 2007 Apr 01
TA  - Molecular Pharmacology
PG  - 1122--1128
VI  - 71
IP  - 4
4099  - http://molpharm.aspetjournals.org/content/71/4/1122.short
4100  - http://molpharm.aspetjournals.org/content/71/4/1122.full
SO  - Mol Pharmacol2007 Apr 01; 71
AB  - 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 phosphatidyl inositol-3 kinase 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 Gαi proteins in primary rat hepatocytes. Treatment of cells with pertussis toxin or expression of dominant-negative Gαi 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 Gαi reduced TCA-induced activation of AKT and of GS in intact rat liver. Together, our findings demonstrate that bile acids are physiological regulators of glycogen synthase in rat liver and that conjugated bile acids use a Gαi-coupled G protein-coupled receptor to regulate GS activity in vitro and in vivo. The American Society for Pharmacology and Experimental Therapeutics