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Research ArticleArticle

An Essential Role of cAMP Response Element Binding Protein in Ginsenoside Rg1-Mediated Inhibition of Na+/Glucose Cotransporter 1 Gene Expression

Chun-Wen Wang, Shih-Chieh Su, Shu-Fen Huang, Yu-Chuan Huang, Fang-Na Chan, Yu-Han Kuo, Mei-Whey Hung, Hang-Chin Lin, Wen-Liang Chang and Tsu-Chung Chang
Molecular Pharmacology December 2015, 88 (6) 1072-1083; DOI: https://doi.org/10.1124/mol.114.097352
Chun-Wen Wang
Graduate Institute of Life Sciences (C.-W.W., T.-C.C.), Department of Biochemistry (S.-C.S., S.-F.H., F.-N.C., Y.-H.K., T.-C.C.), Institute of Preventive Medicine (Y.-C.H.), and School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, Republic of China (H.-C.L., W.-L.C.); Department of Research and Education, Veteran General Hospital, Taipei, Taiwan, Republic of China (M.-W.H.); Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, Republic of China (T.-C.C.); and Department of Biotechnology, Asia University, Taichung, Taiwan, Republic of China (T.-C.C.).
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Shih-Chieh Su
Graduate Institute of Life Sciences (C.-W.W., T.-C.C.), Department of Biochemistry (S.-C.S., S.-F.H., F.-N.C., Y.-H.K., T.-C.C.), Institute of Preventive Medicine (Y.-C.H.), and School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, Republic of China (H.-C.L., W.-L.C.); Department of Research and Education, Veteran General Hospital, Taipei, Taiwan, Republic of China (M.-W.H.); Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, Republic of China (T.-C.C.); and Department of Biotechnology, Asia University, Taichung, Taiwan, Republic of China (T.-C.C.).
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Shu-Fen Huang
Graduate Institute of Life Sciences (C.-W.W., T.-C.C.), Department of Biochemistry (S.-C.S., S.-F.H., F.-N.C., Y.-H.K., T.-C.C.), Institute of Preventive Medicine (Y.-C.H.), and School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, Republic of China (H.-C.L., W.-L.C.); Department of Research and Education, Veteran General Hospital, Taipei, Taiwan, Republic of China (M.-W.H.); Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, Republic of China (T.-C.C.); and Department of Biotechnology, Asia University, Taichung, Taiwan, Republic of China (T.-C.C.).
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Yu-Chuan Huang
Graduate Institute of Life Sciences (C.-W.W., T.-C.C.), Department of Biochemistry (S.-C.S., S.-F.H., F.-N.C., Y.-H.K., T.-C.C.), Institute of Preventive Medicine (Y.-C.H.), and School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, Republic of China (H.-C.L., W.-L.C.); Department of Research and Education, Veteran General Hospital, Taipei, Taiwan, Republic of China (M.-W.H.); Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, Republic of China (T.-C.C.); and Department of Biotechnology, Asia University, Taichung, Taiwan, Republic of China (T.-C.C.).
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Fang-Na Chan
Graduate Institute of Life Sciences (C.-W.W., T.-C.C.), Department of Biochemistry (S.-C.S., S.-F.H., F.-N.C., Y.-H.K., T.-C.C.), Institute of Preventive Medicine (Y.-C.H.), and School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, Republic of China (H.-C.L., W.-L.C.); Department of Research and Education, Veteran General Hospital, Taipei, Taiwan, Republic of China (M.-W.H.); Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, Republic of China (T.-C.C.); and Department of Biotechnology, Asia University, Taichung, Taiwan, Republic of China (T.-C.C.).
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Yu-Han Kuo
Graduate Institute of Life Sciences (C.-W.W., T.-C.C.), Department of Biochemistry (S.-C.S., S.-F.H., F.-N.C., Y.-H.K., T.-C.C.), Institute of Preventive Medicine (Y.-C.H.), and School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, Republic of China (H.-C.L., W.-L.C.); Department of Research and Education, Veteran General Hospital, Taipei, Taiwan, Republic of China (M.-W.H.); Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, Republic of China (T.-C.C.); and Department of Biotechnology, Asia University, Taichung, Taiwan, Republic of China (T.-C.C.).
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Mei-Whey Hung
Graduate Institute of Life Sciences (C.-W.W., T.-C.C.), Department of Biochemistry (S.-C.S., S.-F.H., F.-N.C., Y.-H.K., T.-C.C.), Institute of Preventive Medicine (Y.-C.H.), and School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, Republic of China (H.-C.L., W.-L.C.); Department of Research and Education, Veteran General Hospital, Taipei, Taiwan, Republic of China (M.-W.H.); Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, Republic of China (T.-C.C.); and Department of Biotechnology, Asia University, Taichung, Taiwan, Republic of China (T.-C.C.).
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Hang-Chin Lin
Graduate Institute of Life Sciences (C.-W.W., T.-C.C.), Department of Biochemistry (S.-C.S., S.-F.H., F.-N.C., Y.-H.K., T.-C.C.), Institute of Preventive Medicine (Y.-C.H.), and School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, Republic of China (H.-C.L., W.-L.C.); Department of Research and Education, Veteran General Hospital, Taipei, Taiwan, Republic of China (M.-W.H.); Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, Republic of China (T.-C.C.); and Department of Biotechnology, Asia University, Taichung, Taiwan, Republic of China (T.-C.C.).
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Wen-Liang Chang
Graduate Institute of Life Sciences (C.-W.W., T.-C.C.), Department of Biochemistry (S.-C.S., S.-F.H., F.-N.C., Y.-H.K., T.-C.C.), Institute of Preventive Medicine (Y.-C.H.), and School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, Republic of China (H.-C.L., W.-L.C.); Department of Research and Education, Veteran General Hospital, Taipei, Taiwan, Republic of China (M.-W.H.); Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, Republic of China (T.-C.C.); and Department of Biotechnology, Asia University, Taichung, Taiwan, Republic of China (T.-C.C.).
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Tsu-Chung Chang
Graduate Institute of Life Sciences (C.-W.W., T.-C.C.), Department of Biochemistry (S.-C.S., S.-F.H., F.-N.C., Y.-H.K., T.-C.C.), Institute of Preventive Medicine (Y.-C.H.), and School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, Republic of China (H.-C.L., W.-L.C.); Department of Research and Education, Veteran General Hospital, Taipei, Taiwan, Republic of China (M.-W.H.); Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, Republic of China (T.-C.C.); and Department of Biotechnology, Asia University, Taichung, Taiwan, Republic of China (T.-C.C.).
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Abstract

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) that confers the Rg1-mediated inhibition of SGLT1 gene expression. Chromatin immunoprecipitation assay and targeted CRE-binding protein (CREB) silencing demonstrated that Rg1 reduced the promoter binding of CREB and CREB binding protein 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 the EGFR-CREB signaling pathway in the Rg1-mediated downregulation of SGLT1 expression, which offers a potential strategy in the development of antihyperglycemic and antidiabetic treatments.

Footnotes

    • Received December 24, 2014.
    • Accepted September 23, 2015.
  • This work was supported by grants from the Ministry of Science and Technology of Taiwan, Republic of China [Grants NSC-100-2320-B-016-007, NSC-101-2320-B-016-010-MY2, MOST 103-2320-B-016-005, MOST 104-2320-B-016-013]; and the Ministry of National Defense of Taiwan, Republic of China [Grants MAB-102-9, MAB-103-M019, MAB-104-027].

  • dx.doi.org/10.1124/mol.114.097352.

  • Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 88 (6)
Molecular Pharmacology
Vol. 88, Issue 6
1 Dec 2015
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Research ArticleArticle

Rg1 Reduces SGLT1 Gene Expression via CREB Deactivation

Chun-Wen Wang, Shih-Chieh Su, Shu-Fen Huang, Yu-Chuan Huang, Fang-Na Chan, Yu-Han Kuo, Mei-Whey Hung, Hang-Chin Lin, Wen-Liang Chang and Tsu-Chung Chang
Molecular Pharmacology December 1, 2015, 88 (6) 1072-1083; DOI: https://doi.org/10.1124/mol.114.097352

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Research ArticleArticle

Rg1 Reduces SGLT1 Gene Expression via CREB Deactivation

Chun-Wen Wang, Shih-Chieh Su, Shu-Fen Huang, Yu-Chuan Huang, Fang-Na Chan, Yu-Han Kuo, Mei-Whey Hung, Hang-Chin Lin, Wen-Liang Chang and Tsu-Chung Chang
Molecular Pharmacology December 1, 2015, 88 (6) 1072-1083; DOI: https://doi.org/10.1124/mol.114.097352
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