論文 - 詳細
| RRC ID | 78348 |
|---|---|
| 著者 | Tanaka C, Harada N, Teraoka Y, Urushizaki H, Shinmori Y, Onishi T, Yotsumoto Y, Ito Y, Kitakaze T, Inui T, Murata Y, Inui H, Yamaji R. |
| タイトル | Mogrol stimulates G-protein-coupled bile acid receptor 1 (GPBAR1/TGR5) and insulin secretion from pancreatic β-cells and alleviates hyperglycemia in mice. |
| ジャーナル | Sci Rep |
| Abstract |
Target identification is a crucial step in elucidating the mechanisms by which functional food components exert their functions. Here, we identified the G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5) as a target of the triterpenoid mogrol, a class of aglycone mogroside derivative from Siraitia grosvenorii. Mogrol, but not mogrosides, activated cAMP-response element-mediated transcription in a TGR5-dependent manner. Additionally, mogrol selectively activated TGR5 but not the other bile acid-responsive receptors (i.e., farnesoid X receptor, vitamin D receptor, or muscarinic acetylcholine receptor M3). Several amino acids in TGR5 (L71A2.60, W75AECL1, Q77AECL1, R80AECL1, Y89A3.29, F161AECL2, L166A5.39, Y240A6.51, S247A6.58, Y251A6.62, L262A7.35, and L266A7.39) were found to be important for mogrol-induced activation. Mogrol activated insulin secretion under low-glucose conditions in INS-1 pancreatic β-cells, which can be inhibited by a TGR5 inhibitor. Similar effects of mogrol on insulin secretion were observed in the isolated mouse islets. Mogrol administration partially but significantly alleviated hyperglycemia in KKAy diabetic mice by increasing the insulin levels without affecting the β-cell mass or pancreatic insulin content. These results suggest that mogrol stimulates insulin secretion and alleviates hyperglycemia by acting as a TGR5 agonist. |
| 巻・号 | 14(1) |
| ページ | 3244 |
| 公開日 | 2024-2-8 |
| DOI | 10.1038/s41598-024-53380-x |
| PII | 10.1038/s41598-024-53380-x |
| PMID | 38332164 |
| PMC | PMC10853268 |
| MeSH | Animals Bile Acids and Salts Diabetes Mellitus, Experimental* / metabolism GTP-Binding Proteins / metabolism Hyperglycemia* / drug therapy Insulin / metabolism Insulin Secretion Lanosterol* / analogs & derivatives Mice Phenanthrenes* Receptors, G-Protein-Coupled / genetics Receptors, G-Protein-Coupled / metabolism |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2 |