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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蘇銘嘉(Ming-Jai Su) | |
| dc.contributor.author | Cheng-Yen Tsai | en |
| dc.contributor.author | 蔡政諺 | zh_TW |
| dc.date.accessioned | 2021-06-16T06:35:44Z | - |
| dc.date.available | 2016-10-15 | |
| dc.date.copyright | 2014-10-15 | |
| dc.date.issued | 2014 | |
| dc.date.submitted | 2014-08-01 | |
| dc.identifier.citation | 1.Weng, Y.C., et al., Antihyperglycemic effect of a caffeamide derivative, KS370G, in normal and diabetic mice. J Agric Food Chem, 2010. 58(18): p. 10033-8.
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Paterson, and M. Fisher, Oral antidiabetic agents as cardiovascular drugs. Diabetes Obes Metab, 2007. 9(1): p. 23-30. 16.Witters, L.A., The blooming of the French lilac. J Clin Invest, 2001. 108(8): p. 1105-7. 17.Vigneri, R. and I.D. Goldfine, Role of metformin in treatment of diabetes mellitus. Diabetes Care, 1987. 10(1): p. 118-22. 18.Kim, Y.D., et al., Metformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent regulation of the orphan nuclear receptor SHP. Diabetes, 2008. 57(2): p. 306-14. 19.Collier, C.A., et al., Metformin counters the insulin-induced suppression of fatty acid oxidation and stimulation of triacylglycerol storage in rodent skeletal muscle. Am J Physiol Endocrinol Metab, 2006. 291(1): p. E182-9. 20.Miyazaki, Y., et al., Effect of rosiglitazone on glucose and non-esterified fatty acid metabolism in Type II diabetic patients. Diabetologia, 2001. 44(12): p. 2210-9. 21.Nolan, J.J., et al., Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone. N Engl J Med, 1994. 331(18): p. 1188-93. 22.Yki-Jarvinen, H., Thiazolidinediones. N Engl J Med, 2004. 351(11): p. 1106-18. 23.Bailey, C.J. and C. Day, Review: Thiazolidinediones today. The British Journal of Diabetes & Vascular Disease, 2001. 1(1): p. 7-13. 24.Lebovitz, H.E. and M.N. Feinglos, Sulfonylurea drugs: mechanism of antidiabetic action and therapeutic usefulness. Diabetes Care, 1978. 1(3): p. 189-98. 25.Blickle, J.F., Meglitinide analogues: a review of clinical data focused on recent trials. Diabetes Metab, 2006. 32(2): p. 113-20. 26.Balfour, J.A. and D. McTavish, Acarbose. An update of its pharmacology and therapeutic use in diabetes mellitus. Drugs, 1993. 46(6): p. 1025-54. 27.Nauck, M.A., et al., Incretin-based therapies: viewpoints on the way to consensus. Diabetes Care, 2009. 32 Suppl 2: p. S223-31. 28.Stonehouse, A.H., T. Darsow, and D.G. Maggs, Incretin-based therapies. J Diabetes, 2012. 4(1): p. 55-67. 29.Pijl, H., et al., Bromocriptine: a novel approach to the treatment of type 2 diabetes. Diabetes Care, 2000. 23(8): p. 1154-61. 30.Mikhail, N., Quick-release bromocriptine for treatment of type 2 diabetes. Curr Drug Deliv, 2011. 8(5): p. 511-6. 31.Gruzman, A., G. Babai, and S. Sasson, Adenosine Monophosphate-Activated Protein Kinase (AMPK) as a New Target for Antidiabetic Drugs: A Review on Metabolic, Pharmacological and Chemical Considerations. Rev Diabet Stud, 2009. 6(1): p. 13-36. 32.Hawley, S.A., et al., The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism. Diabetes, 2002. 51(8): p. 2420-5. 33.Winder, W.W. and D.G. Hardie, AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am J Physiol, 1999. 277(1 Pt 1): p. E1-10. 34.Zhou, G., et al., Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest, 2001. 108(8): p. 1167-74. 35.Jamal, M., et al., In vivo formation of salsolinol induced by high acetaldehyde concentration in rat striatum employing microdialysis. Alcohol Alcohol, 2003. 38(3): p. 197-201. 36.Mravec, B., Salsolinol, a derivate of dopamine, is a possible modulator of catecholaminergic transmission: a review of recent developments. Physiol Res, 2006. 55(4): p. 353-64. 37.Naoi, M., et al., Dopamine-derived endogenous N-methyl-(R)-salsolinol: its role in Parkinson's disease. Neurotoxicol Teratol, 2002. 24(5): p. 579-91. 38.Jamal, M., et al., In vivo study of salsolinol produced by a high concentration of acetaldehyde in the striatum and nucleus accumbens of free-moving rats. Alcohol Clin Exp Res, 2003. 27(8 Suppl): p. 79s-84s. 39.Bessesen, D.H., The role of carbohydrates in insulin resistance. J Nutr, 2001. 131(10): p. 2782s-2786s. 40.Holmes, B.F., E.J. Kurth-Kraczek, and W.W. Winder, Chronic activation of 5'-AMP-activated protein kinase increases GLUT-4, hexokinase, and glycogen in muscle. J Appl Physiol (1985), 1999. 87(5): p. 1990-5. 41.Boden, G. and G.I. Shulman, Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and beta-cell dysfunction. Eur J Clin Invest, 2002. 32 Suppl 3: p. 14-23. 42.Lee, Y.S., et al., Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes, 2006. 55(8): p. 2256-64. 43.Kong, W., et al., Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med, 2004. 10(12): p. 1344-51. 44.Zhang, Q., et al., Berberine Moderates Glucose and Lipid Metabolism through Multipathway Mechanism. Evid Based Complement Alternat Med, 2011. 2011. 45.Xie, X., et al., Berberine ameliorates hyperglycemia in alloxan-induced diabetic C57BL/6 mice through activation of Akt signaling pathway. Endocr J, 2011. 58(9): p. 761-8. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/57131 | - |
| dc.description.abstract | 根據中華民國衛生福利部的統計，新陳代謝疾病—糖尿病位居國人十大死因的第五位，其中又以第二型糖尿病患者是較為普見的，而且不僅僅台灣，糖尿病同時也是全球十大死因之一，常會導致神經以及心血管相關的併發症，嚴重的話還可能導致心肌梗塞等等的致命性併發症。且由於人口的增加、邁入老年化社會、都市化、肥胖人數增加、運動減少以及不健康的飲食習慣，導致全球糖尿病患者數預計在西元2025年會達到3億人口。使得開發新的降血糖藥物成為了全球急需處理的問題之一。
Salsolinol，是屬於生物鹼類﹝alkaloid﹞的多巴胺﹝dopamine﹞衍生物，在人體內就有內生性的salsolinol存在，且也可以透過食物的攝取像是香蕉、起司、紅酒等等來獲得，此成分被發現存在於一種具降血糖作用之植物水萃成分中，salsolinol能顯著活化培養細胞﹝C2C12﹞磷酸化腺苷酸依賴蛋白激酶﹝AMPK﹞的表現。在動物體之降血糖作用評估中，發現salsolinol能有效地改善飲食誘發第二型糖尿病小鼠的禁食血糖亦能有效地改善口服葡萄糖耐受性試驗中血糖提升之現象。此外，急性治療試驗中也發現salsolinol能顯著增加胰島素的釋放。另外，在飲食誘發第二型糖尿病小鼠的實驗模式中，每天口服給予10 mg/kg的salsolinol，在經過14天治療後，能顯著的減少血液中的總膽固醇、三酸甘油酯且能有效地增加肝臟以及骨骼肌處之肝醣合成；在脂肪組織部分，salsolinol組之脂肪細胞尺寸以及附睪脂肪占體重百分比都明顯小於負對照組。 因此，基於本篇實驗所發現，我們可以知道salsolinol的降血糖作用可能和磷酸化腺苷酸依賴蛋白激酶﹝AMPK﹞的活化以及促進胰島素釋放有關，雖然salsolinol的詳細的降血糖機制目前尚未明瞭，但由本篇研究的結果可以看到salsolinol具有優秀的潛力在未來能開發成為新的降血糖藥物。 | zh_TW |
| dc.description.abstract | Type 2 diabetes mellitus ( DM ) is a chronic metabolic disorder , whose prevalence has been increasing dramatically all over the world due to population growth , increase in aging population , urbanization and unhealthy diet in high-caloric food . Besides , DM also ranked in the top ten causes of mortality , often leads to neurological complications , myocardial infraction and vascular complications . Therefore , the development of new pharmacological approaches to effectively prevent and treat this metabolic syndrome is of crucial importance .
Salsolinol , an alkolid derivate of dopamine from a herbal plant ( GYT 067 ) , significantly stimulated the phosphorylation on AMPK in C2C12 cells . Salsolinol ( 10 mg/kg ) significantly attenuated the fasting plasma glucose and the elevation of plasma glucose induced by an OGTT in diet-induced type 2 diabetic mice . Besides , the secretion of insulin was significantly increased after the acute treatment with salsolinol . Moreover , after 2-week treatment , salsolinol produced a significant reduction in plasma total cholesterol , plasma triglycerides , adipocyte size and the ratio of epididymal fat weight / body weight . Also , salsolinol significantly increased glycogen synthesis both in skeletal muscle and liver after treatment with salsolinol daily for 2 weeks . Therefore , based on our present study , we conclude that the mechanisms of salsolinol in the hypoglycemic effect may be related to the stimulation of AMPK and increase of insulin release . Although the clear mechanisms for the hypoglycemic activities remain to be determined , the well-characterized antidiabetic effects shown in our study suggest that salsolinol can be a potential agent for the treatment of diabetes in the future . | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T06:35:44Z (GMT). No. of bitstreams: 1 ntu-103-R01443015-1.pdf: 3522467 bytes, checksum: 503a48c722c52dcfb2faebbc182fbc8b (MD5) Previous issue date: 2014 | en |
| dc.description.tableofcontents | Index
口試委員審定書...........I 摘要....................II Abstract...............III Chapter 1 Introduction........1 Chapter 2 Materials and Methods...........................13 2.1 Chemical..............................................13 2.2 Animals...............................................13 2.3 Diet and water composition............................14 2.4 Route of chemicals administration.....................14 2.5 Cell culture..........................................14 2.6 Blood sampling........................................15 2.7 Serum biochemical analysis............................15 2.8 Oral glucose tolerance test (OGTT) ...................16 2.9 Acute drug effect test................................16 2.10 Glycogen content assay...............................17 2.11 Body fat ratio measurements..........................17 2.12 Food consumptions measurements.......................18 2.13 Histological analysis................................18 2.14 Protein extraction and content measurements..........18 2.15 Western blot analysis................................19 2.16 Statistical analysis.................................21 Chapter 3 Results.........................................22 3.1 Effect of salsolinol on AMPK phosphorylation in C2C12 cells.....................................................22 3.2 Acute effect of glybenclamide and salsolinol on OGTT......................................................22 3.3 Subchronic effect of glybenclamide and salsolinol on OGTT......................................................23 3.4 Liver content of glycogen in control , glybenclamide and salsolinol-treated type II diabetic mice..............23 3.5 Skeletal muscle content of glycogen in control , glybenclamide and salsolinol-treated type II diabetic mice......................................................24 3.6 Subchronic effect of glybenclamide and salsolinol on serum TC and TG...........................................24 3.7 Subchronic effect of glybenclamide and salsolinol on adipocyte size............................................24 3.8 Acute effect of glybenclamide and salsolinol on fasting blood glucose and insulin secretion.......................25 3.9 Subchronic effect of glybenclamide and salsolinol on body weight , fat weight and food consumption.............25 Chapter 4 Discussion......................................46 Chapter 5 Future Works....................................49 Chapter 6 References......................................50 Figure and Table Contents Table 1-1 Criteria for the diagnosis of diabetes...........3 Figure 1-1 Metabolic pathways and functions regulated by AMPK......................................................10 Figure 1-2 Biosynthesis of salsolinol.....................12 Figure 3-1 Expressions levels of p-AMPKα/AMPKαprotien in C2C12 cells after treatment with vehicle and salsolinol...27 Figure 3-2 Acute effect of vehicle , glybenclamide and salsolinol on plasma glucose in diet-induced-diabetic mice receiving an oral glucose tolerance test (OGTT)...........28 Figure 3-3 Acute effect of vehicle , glybenclamide and salsolinol on plasma insulin secretion in diet-induced-diabetic mice receiving an oral glucose tolerance test (OGTT)....................................................29 Figure 3-4 Acute effect of vehicle , glybenclamide and salsolinol on plasma glucose area under curve(AUC) in diet-induced-diabetic mice receiving an oral glucose tolerance test (OGTT).....................................30 Figure 3-5 Subchronic effect of glybenclamide and salsolinol on OGTT........................................31 Figure 3-6 Subchronic effect of glybenclamide and salsolinol on OGTT........................................32 Figure 3-7 Subchronic effect of vehicle , glybenclamide and salsolinol on plasma glucose area under curve(AUC) in diet-induced-diabetic mice receiving an oral glucose tolerance test (OGTT).....................................33 Figure 3-8 Liver content of glycogen in control , glybenclamide and salsolinol-treated , diet-induced type II diabetic mice.............................................34 Figure 3-9 Effect of glybenclamide and salsolinol on glycogen synthesis in soleus muscle in diet-induced-diabetic mice.............................................35 Figure 3-10 Subchronic effect of glybenclamide and salsolinol on serum total cholesterol.....................36 Figure 3-11 Subchronic effect of glybenclamide and salsolinol on serum triglycerides.........................37 Figure 3-12,13 Histological analysis of epididymal white adipose tissue from diet-induced-diabetic mice after subchronic treatment......................................38 Figure 3-14 Acute effect of vehicle , glybenclamide and salsolinol on plasma glucose in diet-induced-diabetic mice......................................................40 Figure 3-15 Acute effect of vehicle , glybenclamide and salsolinol on plasma glucose area under curve(AUC) in diet-induced-diabetic mice................................41 Figure 3-16 Acute effect of vehicle , glybenclamide and salsolinol on plasma insulin secretion in diet-induced-diabetic mice.............................................42 Figure 3-17 Growth curves of mice.........................43 Figure 3-18 Fat to body weight ratio after subchronic treatment.................................................44 Figure 3-19 Mean daily food consumption curves of mice....45 | |
| dc.language.iso | en | |
| dc.subject | salsolinol | zh_TW |
| dc.subject | antihyperglycemia | zh_TW |
| dc.subject | diabetic mice | zh_TW |
| dc.subject | AMPK | zh_TW |
| dc.subject | T2DM | zh_TW |
| dc.title | Salsolinol對第二型糖尿病小鼠降血糖作用之研究 | zh_TW |
| dc.title | Hypoglycemic Action of Salsolinol in Type 2 Diabetic Mice | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 102-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳文彬(Wen-Pin Chen),李安生(An-Sheng Lee) | |
| dc.subject.keyword | salsolinol,antihyperglycemia,diabetic mice,AMPK,T2DM, | zh_TW |
| dc.relation.page | 53 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2014-08-01 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥理學研究所 | zh_TW |
| 顯示於系所單位： | 藥理學科所 | |
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