Intestinal Bile Acid Composition Modulates Prohormone Convertase 1/3 (PC1/3) Expression and Consequent GLP-1 Production in Male Mice
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- Kohkichi Morimoto
- Department of Internal Medicine (K.M., T.S., J.-i.I., H.I.), School of Medicine, Keio University, Tokyo 160–8582, Japan
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- Mitsuhiro Watanabe
- Graduate School of Media and Governance (M.W.), Faculty of Environment and Information Studies, Keio University, Kanagawa 252–0882, Japan
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- Taichi Sugizaki
- Department of Internal Medicine (K.M., T.S., J.-i.I., H.I.), School of Medicine, Keio University, Tokyo 160–8582, Japan
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- Jun-ichiro Irie
- Department of Internal Medicine (K.M., T.S., J.-i.I., H.I.), School of Medicine, Keio University, Tokyo 160–8582, Japan
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- Hiroshi Itoh
- Department of Internal Medicine (K.M., T.S., J.-i.I., H.I.), School of Medicine, Keio University, Tokyo 160–8582, Japan
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説明
<jats:title>Abstract</jats:title><jats:p>Besides an established medication for hypercholesterolemia, bile acid binding resins (BABRs) present antidiabetic effects. Although the mechanisms underlying these effects are still enigmatic, glucagon-like peptide-1 (GLP-1) appears to be involved. In addition to a few reported mechanisms, we propose prohormone convertase 1/3 (PC1/3), an essential enzyme of GLP-1 production, as a potent molecule in the GLP-1 release induced by BABRs. In our study, the BABR colestimide leads to a bile acid-specific G protein-coupled receptor TGR5-dependent induction of PC1/3 gene expression. Here, we focused on the alteration of intestinal bile acid composition and consequent increase of total TGR5 agonistic activity to explain the TGR5 activation. Furthermore, we demonstrate that nuclear factor of activated T cells mediates the TGR5-triggered PC1/3 gene expression. Altogether, our data indicate that the TGR5-dependent intestinal PC1/3 gene expression supports the BABR-stimulated GLP-1 release. We also propose a combination of BABR and dipeptidyl peptidase-4 inhibitor in the context of GLP-1-based antidiabetic therapy.</jats:p>
収録刊行物
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- Endocrinology
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Endocrinology 157 (3), 1071-1081, 2016-01-20
The Endocrine Society
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キーワード
- Blood Glucose
- Male
- Blotting, Western
- Fluorescent Antibody Technique
- Gene Expression
- Diet, High-Fat
- Weight Gain
- Receptors, G-Protein-Coupled
- Bile Acids and Salts
- Mice
- Glucagon-Like Peptide 1
- Animals
- Insulin
- RNA, Messenger
- Intestinal Mucosa
- Reverse Transcriptase Polymerase Chain Reaction
- Imidazoles
- Intestines
- Resins, Synthetic
- Proprotein Convertase 1
- Epichlorohydrin
詳細情報 詳細情報について
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- CRID
- 1360004236938613376
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- ISSN
- 19457170
- 00137227
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- PubMed
- 26789236
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE