TY - JOUR T1 - An Essential Role of cAMP Response Element Binding Protein in Ginsenoside Rg1-Mediated Inhibition of Na+/glucose Cotransporter 1 Gene Expression JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.114.097352 SP - mol.114.097352 AU - Chun-Wen Wang AU - Shih-Chieh Su AU - Shu-Fen Huang AU - Yu-Chuan Huang AU - Fang-Na Chan AU - Yu-Han Kuo AU - Mei-Whey Hung AU - Hang-Ching Lin AU - Wen-Liang Chang AU - Tsu-Chung Chang Y1 - 2015/01/01 UR - http://molpharm.aspetjournals.org/content/early/2015/09/30/mol.114.097352.abstract N2 - The Na+/glucose cotransporter 1 (SGLT1) is responsible for glucose uptake in intestinal epithelial cells. It has been shown that the intestinal SGLT1 level is significantly increased in diabetic individuals and positively correlated with the pathogenesis of diabetes. The development of targeted therapeutics that can reduce the intestinal SGLT1 expression level is therefore important. In this study, we showed that ginsenoside Rg1 effectively decreased intestinal glucose uptake through inhibition of SGLT1 gene expression in vivo and in vitro. Transient transfection analysis of the SGLT1 promoter revealed an essential cAMP response element (CRE) which confers the Rg1-mediated inhibition of SGLT1 gene expression. ChIP assay and targeted CREB silencing demonstrated that Rg1 reduced the promoter binding of CRE-binding protein (CREB) and CREB-binding protein (CBP) that is associated with an inactivated chromatin status. In addition, further studies showed that the epidermal growth factor receptor (EGFR) signaling pathway also plays an essential role in the inhibitory effect of Rg1. Taken together, our study demonstrates the involvement of EGFR-CREB signaling pathway in the Rg1-mediated downregulation of SGLT1 expression, which offers a potential strategy in the development of anti-hyperglycemic and anti-diabetic treatments. ER -