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Bile acids enhance the activity of the insulin receptor and glycogen synthase in primary rodent hepatocytes
Author(s) -
Han Song Iy,
Studer Elaine,
Gupta Seema,
Fang Youwen,
Qiao Liang,
Li Weiqun,
Grant Steven,
Hylemon Philip B.,
Dent Paul
Publication year - 2004
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.20043
Subject(s) - glycogen synthase , protein kinase b , insulin receptor , gsk 3 , insulin receptor substrate , medicine , endocrinology , irs1 , insulin like growth factor 1 receptor , insulin , gsk3b , biology , bile acid , chemistry , receptor , signal transduction , biochemistry , insulin resistance , growth factor
Previously, we demonstrated that deoxycholic acid (DCA)‐induced ERK1/2 and AKT signaling in primary hepatocytes is a protective response. In the present study, we examined the regulation of the phosphatidylinositol 3 (PI3) kinase/AKT/glycogen synthase (kinase) 3 (GSK3)/glycogen synthase (GS) pathway by bile acids. In primary hepatocytes, DCA activated ERBB1 (the epidermal growth factor receptor), ERBB2, and the insulin receptor, but not the insulin‐like growth factor 1 (IGF‐1) receptor. DCA‐induced activation of the insulin receptor correlated with enhanced phosphorylation of insulin receptor substrate 1, effects that were both blocked by the insulin receptor inhibitor AG1024 and by expression of the dominant negative IGF‐1 receptor (K1003R), which inhibited in trans . Expression of the dominant negative IGF‐1 receptor (K1003R) also abolished DCA‐induced AKT activation. Bile acid–induced activation of AKT and phosphorylation of GSK3 were blunted by the ERBB1 inhibitor AG1478 and abolished by AG1024. Bile acids caused activation of GS to a similar level induced by insulin (50 nM); both were blocked by inhibition of insulin receptor function and the PI3 kinase/AKT/GSK3 pathway. In conclusion, these findings suggest that bile acids and insulin may cooperate to regulate glucose storage in hepatocytes. (H EPATOLOGY 2004;39:456–463.)