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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃青真(Ching-Jang Huang) | |
| dc.contributor.author | Yi-Ping Pai | en |
| dc.contributor.author | 白依平 | zh_TW |
| dc.date.accessioned | 2021-06-16T23:45:15Z | - |
| dc.date.available | 2017-07-31 | |
| dc.date.copyright | 2012-07-31 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-07-23 | |
| dc.identifier.citation | Albertini, G., Polito, E., Sara, M., Di Gennaro, G., and Onorati, P. (2006). Compulsive masturbation in infantile autism treated by mirtazapine. Pediatr Neurol 34, 417-418.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65474 | - |
| dc.description.abstract | 第二型糖尿病對健康的影響已成為一個重大的公共健康問題。由腸道 L 細胞分泌的 GLP-1 能刺激胰臟 β 細胞分泌胰島素，並增加 β 細胞增生及減少細胞凋亡，並能藉由延遲胃排空而減緩飯後血糖之上升。因此，GLP-1 類似物或其分解酵素 DPP-4 之抑制劑已成為治療糖尿病之藥物之一。近來研究顯示：苦味受器亦表現於 L 細胞及 STC-1 腸內分泌細胞株。本實驗室先前研究顯示，山苦瓜苦味物質粗萃物及苦味物質 denatonium benzoate 能刺激腸道內分泌細胞株 STC-1 細胞分泌 GLP-1。本研究目的為：以腸道內分泌細胞株 STC-1 模式，篩選偵測不同山苦瓜萃物及其水解物促進 GLP-1 分泌之活性，並測試一些已知之苦味分子是否亦能刺激此細胞分泌 GLP-1。
實驗結果發現，山苦瓜水萃物及富含苦味物質之區分物具有最佳之活性。而除了強酸水解萃物 2Ba15-E 及 3Ba18-E 外，其他萃物水解後之有機溶劑萃物亦具活性。純化合物方面，苦瓜所含之 karavilagenin E 及 oleanolic acid 亦具活性，但人參之 ginsenoside Re 則否。已知 oleanolic acid 為膽酸膜受器 TGR5 之 agonist，推測其可能透過此受器促進 STC-1 分泌 GLP-1。所測試之苦味化合物中，高濃度下具有苦味之人工甜味劑 acesulfame K、saccharin，以及苦味分子 chloroquine、brucine、denatonium benzoate、quinine、caffeine、strychnine、allyl isothiocyanate、limonin 均具有促進腸道內分泌細胞分泌 GLP-1 之活性，salicin 及 phenylthiocarbamide 則否。其中，可專一性活化 TAS2R38 苦味受器之 allyl isothiocyanate 具最佳之活性，然此活性可被 probenecid 所抑制。Probenecid 為 TAS2R16 與 TAS2R38 之 allosteric inhibitor，意味 allyl isothiocyanate 促進 GLP-1 分泌之作用係透過苦味受器 TAS2R38。另一方面，probenecid 亦可部分抑制山苦瓜水萃物及山苦瓜苦味物質粗萃物促進腸道內分泌細胞分泌 GLP-1 之活性，推測山苦瓜中可能含有苦味受器 TAS2R16 或 TAS2R38 之 agonist，並透過苦味受器刺激 GLP-1 分泌。 綜之，本研究結果顯示山苦瓜水萃物、富含苦味物質之區分物及多數之水解萃物以及十種已知苦味物質皆能刺激 GLP-1 分泌。苦味抑制劑添加後對數種樣品之抑制現象，顯示部分苦味物質可能透過腸內分泌細胞之苦味受器之作用，促進 GLP-1 之分泌，對血糖調控有所助益。 | zh_TW |
| dc.description.abstract | The prevalence of type 2 diabetes and impaired glucose homeostasis have become a significant public health concern. Glucagon-like peptide-1 (GLP-1) secreted by intestinal L cells is an enteric hormone that stimulates insulin secretion, increase the β cell proliferation, decreased β cell apoptosis, and slow down the rise in postprandial plasma glucose by delayed gastric emptying. Thus, GLP-1 receptor agonists and DPP-4 inhibitors have been introduced as the newest class of glucose-lowering agents for the treatment of type 2 diabetes mellitus. The intestinal L cells and the enteroendocrine cell line, STC-1, have been shown to express bitter taste receptors (T2Rs). Previous findings in our laboratory revealed that the crude bitter extract of bitter gourd (BGP-bi) and denatonium benzoate could enhance GLP-1 secretion in STC-1 cells. We hypothesized that one of the mechanisms for the hypoglycemic effect of BG might be through enhancing GLP-1 secretion in the enteroendocrine cells via T2Rs.
Treatment with Water Extract(WE) and BGP-bi resulted in the highest GLP-1 secretion in the STC-1 cells. Except for the 2 extracts of strong acid hydrolysates, 2Ba15-E and 3Ba18-E, most extracts of hydrolyzed products also had this activity. Karavilagenin E and oleanolic acid, two pure triterpenoid compounds from BG were also active, but not ginsenoside Re. The oleanolic acid is an agonist of TGR5, a bile acid receptor expressed in the STC-1 cells. This receptor might contribute, at least in part, to its activity. Among bitter compounds tested, acesulfame K, saccharin, chloroquine, brucine, denatonium benzoate, quinine, caffeine, strychnine, allyl isothiocyanate, limoin could stimulate GLP-1, but not salicin and phenylthiocarbamide. Among these, allyl isothiocyanate showed highest activity. As this compound is a specific agonist of TAS2R38, ad its activity could be inhibited by probenecid, an allosteric inhibitor of TAS2R16 and TAS2R38, the stimulation of GLP-1 secretion by allyl isothiocyanate might be through TAS2R38. Moreover, probenecid also partially inhibited GLP-1 secretion of BG WE and bitter enriched fraction, suggesting these BG extracts might contain agonists of TAS2R16 or TAS2R38 and stimulate GLP-1 secretion through these receptors. In conclusion, water extracts, bitter rich fractions, most hydrolyzed extracts, Karavilagenin E and oleanolic acid from BG and 10 bitter compounds have been shown to stimulate GLP-1 secretion in STC-1 cells. Based on the fact that the stimulation could be inhibited by a specific inhibitor of taste receptor, it is concluded that bitter taste receptors might be involved in the GLP-1 secretion of STC-1 cells stimulated by bitter compounds, including those in bitter gourd. It would be interested to further study the glucose regulation potential of these bitter compounds as well. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T23:45:15Z (GMT). No. of bitstreams: 1 ntu-101-R99b22045-1.pdf: 3455048 bytes, checksum: 00b812a8c2a199f89c31268fe0697fd4 (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | 總目錄
第一章 緒論 1 第一節 研究動機與目的 1 第二節 文獻回顧 2 一、 第二型糖尿病與代謝症候群 2 二、 Glucagon-like peptide-1 (GLP-1) 4 三、 GLP-1 與第二型糖尿病之治療 11 四、 苦味 (Bitter taste) 14 五、 苦瓜 19 第三節 研究假說與實驗架構 22 一、 研究假說 22 二、 實驗架構 22 第二章 山苦瓜萃物暨其區分物對腸道內分泌細胞株 STC-1分泌 GLP-1 之影響 23 第一節 前言 23 第二節 材料與方法 24 一、 細胞株 24 二、 試劑 24 三、 儀器設備 25 四、 山苦瓜萃物既其區分物之製備 26 五、 實驗流程 29 六、 數據整理與統計分析 31 第三節 結果 31 第四節 討論 43 一、 山苦瓜經 β-glucosidase 酵素或不同酸水解條件後，對腸道內分泌細胞 STC-1 分泌 GLP-1 之影響 43 二、 山苦瓜刺激腸道內分泌細胞分泌 GLP-1 之可能成分 45 三、 山苦瓜刺激腸道內分泌細胞分泌 GLP-1 之可能機制 47 第五節 結論 47 第三章 苦味物質對腸道內分泌細胞株 STC-1 分泌 GLP-1 之影響 49 第一節 前言 49 第二節 材料與方法 51 一、 細胞株 51 二、 試劑 51 三、 儀器設備 51 四、 苦味化合物、苦味遮蔽劑、苦味受器及苦味訊息傳遞分子 PLC 之抑制劑 51 五、 花蓮四號山苦瓜水萃物及苦味物質粗萃物之製備 56 六、 實驗流程 56 七、 數據統計 56 第三節 結果 57 第四節 討論 71 一、 苦味分子對腸道內分泌細胞 GLP-1 分泌之調控 71 二、 山苦瓜中苦味物質對腸道內分泌細胞 GLP-1 分泌之調控 72 三、 TRPV1 對腸道內分泌細胞 GLP-1 分泌之調控 74 第五節 結論 74 第四章 綜合討論與總結論 76 第一節 綜合討論 76 第二節 總結論 79 第五章 參考文獻 80 表目錄 表 1-1 我國代謝症候群判定之標準 3 表 1-2 糖尿病前期與糖尿病判定之標準 3 表 1-3 第二型糖尿病藥物作用原理與其副作用-1 12 表 1-4 已上市或進入人體臨床試驗之 GLP-1 RECEPTOR AGONIST 13 表 2-1 山苦瓜各萃物或化合物刺激與抑制 STC-1 細胞分泌 GLP-1 之最大倍數總整理 42 表 3-1 小鼠與人類間具有同源性 (ORTHOLOGY) 之苦味受器及本實驗中所使用之苦味分子 53 表 3-2-1 苦味物質刺激與抑制 STC-1 細胞分泌 GLP-1 之最大倍數總整理 64 表 3-2-2 苦味物質刺激與抑制 STC-1 細胞分泌 GLP-1 之最大倍數總整理 65 表 4-1 目前已知苦味受器 TAS2R38 之 AGONIST 78 圖目錄 圖 1-1 GLP-1 之胺基酸序列 5 圖 1-2 PREPROGLUCAGON 基因的表現 5 圖 1-3 腸道 L 細胞分泌 GLP-1 之機制 6 圖 1-4 腸道內分泌細胞中由 GPCR 所調控之營養感測 9 圖 1-5 透過 GLP-1R 調控胰臟 β 細胞訊息之傳遞 10 圖 1-6 GLP-1 於周邊組織之作用 10 圖 1-7 味覺認知機制 14 圖 1-8 味覺細胞中苦味分子之訊息傳遞機制 15 圖 1-9 味覺受器細胞、味蕾及味乳頭 16 圖 1-10 TYPE 1 TASTE RECEPTORS 及 TYPE 2 TASTE RECEPTORS 在各組織中之表現 17 圖 1-11 T1R、T2R 味覺受器之結構及其基因 18 圖 1-12 苦瓜於不同組織及器官之作用 19 圖 1-13 花蓮縣吉安鄉花蓮改良場所提供之山苦瓜 21 圖 1-14 (1)苦瓜苦味物質：MOMORDICOSIDE L (R = H) 和 MOMORDICOSIDE K (R = ME)；(2) 苦瓜中具有降血糖活性之三萜類化合物：3β,7β,25-TRIHYDROXYCUCURBITA-5,23(E)-DIEN-19-AL 21 圖 2-1 山苦瓜分離出之三萜類化合物 COMPOUND 6 28 圖 2-2 山苦瓜區分流程 36 圖 2-3 花蓮二號山苦瓜全果果汁萃物 H2J 及花蓮三號山苦瓜全果果汁萃物 H3J 對 STC-1 細胞分泌 GLP-1 之影響 37 圖 2-4 (A) 花蓮二號山苦瓜正丁醇萃物 H2JB 與其酵素水解後之產物 2BE-E/2BE-B、弱酸水解之產物 2BA15-H/2BA15-E 對 STC-1 細胞分泌 GLP-1 之影響 (B) 花蓮三號山苦瓜正丁醇萃物 H3JB 與其酵素水解後之產物 3BE-E/3BE-B 及酸水解之產物對 STC-1 細胞分泌 GLP-1 之影響 38 圖 2-5 花蓮三號山苦瓜正丁醇萃物之不同條件酸水解萃物對 STC-1 細胞分泌 GLP-1 之影響 39 圖 2-6 花蓮四號苦瓜 (A) 水萃物 H4WE (B) 苦味物質粗萃物 BGP-BI 對 STC-1 細胞分泌 GLP-1 之影響 39 圖 2-7 (A) 苦瓜分離出之三萜類化合物 COMPOUND 6 對 STC-1 細胞分泌 GLP-1 之影響 (B) COMPOUND 6 之結構 40 圖 2-8 (A) OLEANOLIC ACID (B) GINSENOSIDE RE 對 STC-1 細胞分泌 GLP-1 之影響、(C) OLEANOLIC ACID (D) GINSENOSIDE RE 之結構 41 圖 2-9 化合物 3 及化合物 5 之結構 44 圖 2-10 (A) 葫蘆烷型及 (B) 齊墩果烷型三萜類化合物之基本結構 46 圖 2-11 腸道的內分泌細胞與舌頭的味覺受體細胞之訊息傳遞機制 48 圖 3-1 甜味、鮮味及苦味之味覺受器與其訊息傳遞機制 50 圖 3-2 以小鼠及人類 T2R 蛋白質全長所建構之演化樹 54 圖 3-3 苦味物質 (A) CAFFEINE (B) DENATONIUM BENZOATE 及人工甘味劑 (C) ACESULFAME K (D) SACCHARIN對 STC-1 細胞分泌 GLP-1 之影響 61 圖 3-4 苦味物質對 STC-1 細胞分泌 GLP-1 之影響：(A) BRUCINE (B) CHLOROQUINE (C) SALICIN (D) STRYCHNINE 62 圖 3-5 苦味物質對 STC-1 細胞分泌 GLP-1 之影響：(A) LIMONIN (B) ALLYL ISOTHIOCYANATE (C) PHENYLTHIOCARBAMIDE (D) QUININE 63 圖 3-6 共同投予苦味物質 ALLYL ISOTHIOCYANATE 與苦味抑制劑 PROBENECID 對 STC-1 細胞分泌 GLP-1 之影響 66 圖 3-7 共同投予苦味物質 SACCHARIN 與(A)苦味遮蔽劑 FERULIC ACID、(B) 苦味抑制劑 PROBENECID 或 PLC 抑制劑 U73122 對 STC-1 細胞分泌 GLP-1 之影響 67 圖 3-8 共同投予苦瓜水萃物 H4WE 與苦味抑制劑 PROBENECID 或 PLC 抑制劑 U73122 對 STC-1 細胞分泌 GLP-1 之影響 68 圖 3-9 共同投予苦瓜苦味物質 BGP-BI 與苦味抑制劑 PROBENECID 或 PLC 抑制劑 U73122 對 STC-1 細胞分泌 GLP-1 之影響 69 圖 3-10 山苦瓜室溫水萃物及熱水萃物對 STC-1 細胞分泌 GLP-1 之影響 70 圖 3-11 TRPV1 AGONIST CAPSACIN 對 STC-1 細胞分泌 GLP-1 之影響 70 圖 3-12 雪膽中三萜類化合物之結構與味覺 73 | |
| dc.language.iso | zh-TW | |
| dc.subject | 苦瓜 | zh_TW |
| dc.subject | 苦味 | zh_TW |
| dc.subject | 腸道內分泌細胞 | zh_TW |
| dc.subject | GLP-1 | zh_TW |
| dc.subject | 血糖調控 | zh_TW |
| dc.subject | blood glucose homeostasis | en |
| dc.subject | bitter taste | en |
| dc.subject | enteroendocrine STC-1 cells | en |
| dc.subject | glucagon-like peptide-1 | en |
| dc.subject | bitter gourd | en |
| dc.title | 山苦瓜萃物暨其區分物及一些苦味分子對腸道內分泌細胞株 STC-1 分泌 GLP-1 之影響 | zh_TW |
| dc.title | The effects of Momordica charantia L. extracts and some bitter compounds on the GLP-1 secretion of the enteroendocrine STC-1 cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 李昆達,林璧鳳,楊健志,蕭明熙 | |
| dc.subject.keyword | 苦瓜,苦味,腸道內分泌細胞,GLP-1,血糖調控, | zh_TW |
| dc.subject.keyword | bitter gourd,bitter taste,enteroendocrine STC-1 cells,glucagon-like peptide-1,blood glucose homeostasis, | en |
| dc.relation.page | 91 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2012-07-24 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科技學系 | zh_TW |
| 顯示於系所單位： | 生化科技學系 | |
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