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A gut microbial metabolite of ginsenosides, compound K, induces intestinal glucose absorption and Na + /glucose cotransporter 1 gene expression through activation of cAMP response element binding protein
Author(s) -
Wang ChunWen,
Huang YuChuan,
Chan FangNa,
Su ShihChieh,
Kuo YuHan,
Huang ShuFen,
Hung MeiWhey,
Lin HangChin,
Chang WenLiang,
Chang TsuChung
Publication year - 2015
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201400688
Subject(s) - creb , cotransporter , gene expression , response element , signal transduction , chemistry , microbiology and biotechnology , biology , transcription factor , biochemistry , promoter , gene , organic chemistry , sodium
Scope The Na + /glucose cotransporter 1 (SGLT1) plays a crucial role in glucose uptake in intestinal epithelial cells (IECs), which has been shown essential in ameliorating intestinal inflammation. Ginseng has historically been used to treat inflammatory disorders. Understanding the regulatory mechanism of ginseng‐mediated induction of SGLT1 gene expression in human intestinal cells is therefore important. Methods and results We demonstrate that ginsenoside compound K (CK) enhances SGLT1‐mediated glucose uptake in mice and human intestinal Caco‐2 cells. Transient transfection analysis using SGLT1 promoter‐luciferase reporters demonstrated that the presence of an essential cAMP response element (CRE) is required for CK‐mediated induction of SGLT1 gene expression. The ChIP assays indicated that increased CRE‐binding protein (CREB) and CREB‐binding protein (CBP) binding to the SGLT1 promoter in CK‐treated cells is associated with an activated chromatin state. Our result showed that the increased CREB phosphorylation is directly correlated with SGLT1 expression in IECs. Further studies indicated that the epidermal growth factor receptor (EGFR) signaling pathway is involved in the CK‐mediated effect. Conclusion These findings provide a novel mechanism for the CK‐mediated upregulation of SGLT1 expression through EGFR‐CREB signaling activation, which could contribute to reducing gut inflammation.