請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/62828完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃青真 | |
| dc.contributor.author | Kan-Ni Lu | en |
| dc.contributor.author | 呂侃霓 | zh_TW |
| dc.date.accessioned | 2021-06-16T16:11:42Z | - |
| dc.date.available | 2018-02-01 | |
| dc.date.copyright | 2013-03-06 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2013-02-18 | |
| dc.identifier.citation | References
1. Ismail-Beigi F. Clinical practice. Glycemic management of type 2 diabetes mellitus. N Engl J Med. 2012 Apr 5;366:1319-27. 2. Pearson J, Powers MA. Systematically initiating insulin: the staged diabetes management approach. Diabetes Educ. 2006 Jan-Feb;32:19S-28S. 3. Chao CY, Huang CJ. Bitter gourd (Momordica charantia) extract activates peroxisome proliferator-activated receptors and upregulates the expression of the acyl CoA oxidase gene in H4IIEC3 hepatoma cells. J Biomed Sci. 2003 Nov-Dec;10:782-91. 4. Chao CY, Yin MC, Huang CJ. Wild bitter gourd extract up-regulates mRNA expression of PPARalpha, PPARgamma and their target genes in C57BL/6J mice. J Ethnopharmacol. 2011 Apr 26;135:156-61. 5. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985 Jul;28:412-9. 6. Storlien L, Oakes ND, Kelley DE. Metabolic flexibility. Proc Nutr Soc. 2004 May;63:363-8. 7. Hamid M, McCluskey JT, McClenaghan NH, Flatt PR. Comparison of the secretory properties of four insulin-secreting cell lines. Endocr Res. 2002 Feb-May;28:35-47. 8. Doyle ME, Egan JM. Pharmacological agents that directly modulate insulin secretion. Pharmacol Rev. 2003 Mar;55:105-31. 9. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003 Jan;52:102-10. 10. Rahier J, Guiot Y, Goebbels RM, Sempoux C, Henquin JC. Pancreatic beta-cell mass in European subjects with type 2 diabetes. Diabetes Obes Metab. 2008 Nov;10 Suppl 4:32-42. 11. Fariss MW, Chan CB, Patel M, Van Houten B, Orrenius S. Role of mitochondria in toxic oxidative stress. Mol Interv. 2005 Apr;5:94-111. 12. Krauss S, Zhang CY, Scorrano L, Dalgaard LT, St-Pierre J, Grey ST, Lowell BB. Superoxide-mediated activation of uncoupling protein 2 causes pancreatic beta cell dysfunction. J Clin Invest. 2003 Dec;112:1831-42. 13. Echtay KS, Roussel D, St-Pierre J, Jekabsons MB, Cadenas S, Stuart JA, Harper JA, Roebuck SJ, Morrison A, et al. Superoxide activates mitochondrial uncoupling proteins. Nature. 2002 Jan 3;415:96-9. 14. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993 Jan 1;259:87-91. 15. Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS. Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature. 1997 Oct 9;389:610-4. 16. Dandona P, Weinstock R, Thusu K, Abdel-Rahman E, Aljada A, Wadden T. Tumor necrosis factor-alpha in sera of obese patients: fall with weight loss. J Clin Endocrinol Metab. 1998 Aug;83:2907-10. 17. Paz K, Hemi R, LeRoith D, Karasik A, Elhanany E, Kanety H, Zick Y. A molecular basis for insulin resistance. Elevated serine/threonine phosphorylation of IRS-1 and IRS-2 inhibits their binding to the juxtamembrane region of the insulin receptor and impairs their ability to undergo insulin-induced tyrosine phosphorylation. J Biol Chem. 1997 Nov 21;272:29911-8. 18. Aguirre V, Uchida T, Yenush L, Davis R, White MF. The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307). J Biol Chem. 2000 Mar 24;275:9047-54. 19. Dinarello CA. Blocking IL-1 in systemic inflammation. J Exp Med. 2005 May 2;201:1355-9. 20. Matsuki T, Horai R, Sudo K, Iwakura Y. IL-1 plays an important role in lipid metabolism by regulating insulin levels under physiological conditions. J Exp Med. 2003 Sep 15;198:877-88. 21. Jager J, Gremeaux T, Cormont M, Le Marchand-Brustel Y, Tanti JF. Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology. 2007 Jan;148:241-51. 22. Kopp HP, Kopp CW, Festa A, Krzyzanowska K, Kriwanek S, Minar E, Roka R, Schernthaner G. Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler Thromb Vasc Biol. 2003 Jun 1;23:1042-7. 23. Kahn BB. Lilly lecture 1995. Glucose transport: pivotal step in insulin action. Diabetes. 1996 Nov;45:1644-54. 24. Kelley DE, Goodpaster B, Wing RR, Simoneau JA. Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss. Am J Physiol. 1999 Dec;277:E1130-41. 25. Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet. 1963 Apr 13;1:785-9. 26. Jucker BM, Rennings AJ, Cline GW, Shulman GI. 13C and 31P NMR studies on the effects of increased plasma free fatty acids on intramuscular glucose metabolism in the awake rat. J Biol Chem. 1997 Apr 18;272:10464-73. 27. Cline GW, Petersen KF, Krssak M, Shen J, Hundal RS, Trajanoski Z, Inzucchi S, Dresner A, Rothman DL, Shulman GI. Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes. N Engl J Med. 1999 Jul 22;341:240-6. 28. Dresner A, Laurent D, Marcucci M, Griffin ME, Dufour S, Cline GW, Slezak LA, Andersen DK, Hundal RS, et al. Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. J Clin Invest. 1999 Jan;103:253-9. 29. Griffin ME, Marcucci MJ, Cline GW, Bell K, Barucci N, Lee D, Goodyear LJ, Kraegen EW, White MF, Shulman GI. Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade. Diabetes. 1999 Jun;48:1270-4. 30. Krssak M, Falk Petersen K, Dresner A, DiPietro L, Vogel SM, Rothman DL, Roden M, Shulman GI. Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetologia. 1999 Jan;42:113-6. 31. Yu C, Chen Y, Cline GW, Zhang D, Zong H, Wang Y, Bergeron R, Kim JK, Cushman SW, et al. Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem. 2002 Dec 27;277:50230-6. 32. Kim JK, Fillmore JJ, Chen Y, Yu C, Moore IK, Pypaert M, Lutz EP, Kako Y, Velez-Carrasco W, et al. Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. Proc Natl Acad Sci U S A. 2001 Jun 19;98:7522-7. 33. Merkel M, Weinstock PH, Chajek-Shaul T, Radner H, Yin B, Breslow JL, Goldberg IJ. Lipoprotein lipase expression exclusively in liver. A mouse model for metabolism in the neonatal period and during cachexia. J Clin Invest. 1998 Sep 1;102:893-901. 34. Falcon A, Doege H, Fluitt A, Tsang B, Watson N, Kay MA, Stahl A. FATP2 is a hepatic fatty acid transporter and peroxisomal very long-chain acyl-CoA synthetase. Am J Physiol Endocrinol Metab. 2010 Sep;299:E384-93. 35. Doege H, Grimm D, Falcon A, Tsang B, Storm TA, Xu H, Ortegon AM, Kazantzis M, Kay MA, Stahl A. Silencing of hepatic fatty acid transporter protein 5 in vivo reverses diet-induced non-alcoholic fatty liver disease and improves hyperglycemia. J Biol Chem. 2008 Aug 8;283:22186-92. 36. Lee HY, Birkenfeld AL, Jornayvaz FR, Jurczak MJ, Kanda S, Popov V, Frederick DW, Zhang D, Guigni B, et al. Apolipoprotein CIII overexpressing mice are predisposed to diet-induced hepatic steatosis and hepatic insulin resistance. Hepatology. 2011 Nov;54:1650-60. 37. Zhang D, Liu ZX, Choi CS, Tian L, Kibbey R, Dong J, Cline GW, Wood PA, Shulman GI. Mitochondrial dysfunction due to long-chain Acyl-CoA dehydrogenase deficiency causes hepatic steatosis and hepatic insulin resistance. Proc Natl Acad Sci U S A. 2007 Oct 23;104:17075-80. 38. Nagle CA, An J, Shiota M, Torres TP, Cline GW, Liu ZX, Wang S, Catlin RL, Shulman GI, et al. Hepatic overexpression of glycerol-sn-3-phosphate acyltransferase 1 in rats causes insulin resistance. J Biol Chem. 2007 May 18;282:14807-15. 39. Turinsky J, O'Sullivan DM, Bayly BP. 1,2-Diacylglycerol and ceramide levels in insulin-resistant tissues of the rat in vivo. J Biol Chem. 1990 Oct 5;265:16880-5. 40. Kaku K, Fiedorek FT, Jr., Province M, Permutt MA. Genetic analysis of glucose tolerance in inbred mouse strains. Evidence for polygenic control. Diabetes. 1988 Jun;37:707-13. 41. Kooptiwut S, Zraika S, Thorburn AW, Dunlop ME, Darwiche R, Kay TW, Proietto J, Andrikopoulos S. Comparison of insulin secretory function in two mouse models with different susceptibility to beta-cell failure. Endocrinology. 2002 Jun;143:2085-92. 42. Toye AA, Lippiat JD, Proks P, Shimomura K, Bentley L, Hugill A, Mijat V, Goldsworthy M, Moir L, et al. A genetic and physiological study of impaired glucose homeostasis control in C57BL/6J mice. Diabetologia. 2005 Apr;48:675-86. 43. Surwit RS, Feinglos MN, Rodin J, Sutherland A, Petro AE, Opara EC, Kuhn CM, Rebuffe-Scrive M. Differential effects of fat and sucrose on the development of obesity and diabetes in C57BL/6J and A/J mice. Metabolism. 1995 May;44:645-51. 44. Burcelin R, Crivelli V, Dacosta A, Roy-Tirelli A, Thorens B. Heterogeneous metabolic adaptation of C57BL/6J mice to high-fat diet. Am J Physiol Endocrinol Metab. 2002 Apr;282:E834-42. 45. Rossmeisl M, Rim JS, Koza RA, Kozak LP. Variation in type 2 diabetes--related traits in mouse strains susceptible to diet-induced obesity. Diabetes. 2003 Aug;52:1958-66. 46. Kayo T, Fujita H, Nozaki J, E X, Koizumi A. Identification of two chromosomal loci determining glucose intolerance in a C57BL/6 mouse strain. Comp Med. 2000 Jun;50:296-302. 47. Sekar DS, Sivagnanam K, Subramanian S. Antidiabetic activity of Momordica charantia seeds on streptozotocin induced diabetic rats. Pharmazie. 2005 May;60:383-7. 48. Ahmed I, Adeghate E, Cummings E, Sharma AK, Singh J. Beneficial effects and mechanism of action of Momordica charantia juice in the treatment of streptozotocin-induced diabetes mellitus in rat. Mol Cell Biochem. 2004 Jun;261:63-70. 49. Kumar Shetty A, Suresh Kumar G, Veerayya Salimath P. Bitter gourd (Momordica charantia) modulates activities of intestinal and renal disaccharidases in streptozotocin-induced diabetic rats. Mol Nutr Food Res. 2005 Aug;49:791-6. 50. Miura T, Itoh C, Iwamoto N, Kato M, Kawai M, Park SR, Suzuki I. Hypoglycemic activity of the fruit of the Momordica charantia in type 2 diabetic mice. J Nutr Sci Vitaminol (Tokyo). 2001 Oct;47:340-4. 51. Grover JK, Rathi SS, Vats V. Amelioration of experimental diabetic neuropathy and gastropathy in rats following oral administration of plant (Eugenia jambolana, Mucuna pruriens and Tinospora cordifolia) extracts. Indian J Exp Biol. 2002 Mar;40:273-6. 52. Chuang CY, Hsu C, Chao CY, Wein YS, Kuo YH, Huang CJ. Fractionation and identification of 9c, 11t, 13t-conjugated linolenic acid as an activator of PPARalpha in bitter gourd (Momordica charantia L.). J Biomed Sci. 2006 Nov;13:763-72. 53. Brozinick JT, Jr., Roberts BR, Dohm GL. Defective signaling through Akt-2 and -3 but not Akt-1 in insulin-resistant human skeletal muscle: potential role in insulin resistance. Diabetes. 2003 Apr;52:935-41. 54. Kanety H, Feinstein R, Papa MZ, Hemi R, Karasik A. Tumor necrosis factor alpha-induced phosphorylation of insulin receptor substrate-1 (IRS-1). Possible mechanism for suppression of insulin-stimulated tyrosine phosphorylation of IRS-1. J Biol Chem. 1995 Oct 6;270:23780-4. 55. Larsen CM, Faulenbach M, Vaag A, Volund A, Ehses JA, Seifert B, Mandrup-Poulsen T, Donath MY. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007 Apr 12;356:1517-26. 56. He J, Usui I, Ishizuka K, Kanatani Y, Hiratani K, Iwata M, Bukhari A, Haruta T, Sasaoka T, Kobayashi M. Interleukin-1alpha inhibits insulin signaling with phosphorylating insulin receptor substrate-1 on serine residues in 3T3-L1 adipocytes. Mol Endocrinol. 2006 Jan;20:114-24. 57. Weigert C, Hennige AM, Brodbeck K, Haring HU, Schleicher ED. Interleukin-6 acts as insulin sensitizer on glycogen synthesis in human skeletal muscle cells by phosphorylation of Ser473 of Akt. Am J Physiol Endocrinol Metab. 2005 Aug;289:E251-7. 58. Steensberg A, Keller C, Starkie RL, Osada T, Febbraio MA, Pedersen BK. IL-6 and TNF-alpha expression in, and release from, contracting human skeletal muscle. Am J Physiol Endocrinol Metab. 2002 Dec;283:E1272-8. 59. Kamohara S, Burcelin R, Halaas JL, Friedman JM, Charron MJ. Acute stimulation of glucose metabolism in mice by leptin treatment. Nature. 1997 Sep 25;389:374-7. 60. Oral EA, Simha V, Ruiz E, Andewelt A, Premkumar A, Snell P, Wagner AJ, DePaoli AM, Reitman ML, et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med. 2002 Feb 21;346:570-8. 61. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA. The hormone resistin links obesity to diabetes. Nature. 2001 Jan 18;409:307-12. 62. Banerjee RR, Rangwala SM, Shapiro JS, Rich AS, Rhoades B, Qi Y, Wang J, Rajala MW, Pocai A, et al. Regulation of fasted blood glucose by resistin. Science. 2004 Feb 20;303:1195-8. 63. Graham TE, Yang Q, Bluher M, Hammarstedt A, Ciaraldi TP, Henry RR, Wason CJ, Oberbach A, Jansson PA, et al. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N Engl J Med. 2006 Jun 15;354:2552-63. 64. Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, Kotani K, Quadro L, Kahn BB. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature. 2005 Jul 21;436:356-62. 65. Uebanso T, Arai H, Taketani Y, Fukaya M, Yamamoto H, Mizuno A, Uryu K, Hada T, Takeda E. Extracts of Momordica charantia suppress postprandial hyperglycemia in rats. J Nutr Sci Vitaminol (Tokyo). 2007 Dec;53:482-8. 66. Mahomoodally MF, Gurib-Fakim A, Subratty AH. Effect of exogenous ATP on Momordica charantia Linn. (Cucurbitaceae) induced inhibition of D-glucose, L-tyrosine and fluid transport across rat everted intestinal sacs in vitro. J Ethnopharmacol. 2007 Mar 21;110:257-63. 67. Hafizur RM, Kabir N, Chishti S. Modulation of pancreatic beta-cells in neonatally streptozotocin-induced type 2 diabetic rats by the ethanolic extract of Momordica charantia fruit pulp. Nat Prod Res. 2011 Feb;25:353-67. 68. Nivitabishekam SN, Asad M, Prasad VS. Pharmacodynamic interaction of Momordica charantia with rosiglitazone in rats. Chem Biol Interact. 2009 Feb 12;177:247-53. 69. Han C, Hui Q, Wang Y. Hypoglycaemic activity of saponin fraction extracted from Momordica charantia in PEG/salt aqueous two-phase systems. Nat Prod Res. 2008;22:1112-9. 70. Keller AC, Ma J, Kavalier A, He K, Brillantes AM, Kennelly EJ. Saponins from the traditional medicinal plant Momordica charantia stimulate insulin secretion in vitro. Phytomedicine. 2011 Dec 15;19:32-7. 71. Tan MJ, Ye JM, Turner N, Hohnen-Behrens C, Ke CQ, Tang CP, Chen T, Weiss HC, Gesing ER, et al. Antidiabetic activities of triterpenoids isolated from bitter melon associated with activation of the AMPK pathway. Chem Biol. 2008 Mar;15:263-73. 72. Wang ZQ, Zhang XH, Yu Y, Poulev A, Ribnicky D, Floyd ZE, Cefalu WT. Bioactives from bitter melon enhance insulin signaling and modulate acyl carnitine content in skeletal muscle in high-fat diet-fed mice. J Nutr Biochem. 2011 Nov;22:1064-73. 73. Cheng HL, Huang HK, Chang CI, Tsai CP, Chou CH. A cell-based screening identifies compounds from the stem of Momordica charantia that overcome insulin resistance and activate AMP-activated protein kinase. J Agric Food Chem. 2008 Aug 27;56:6835-43. 74. Shih CC, Lin CH, Lin WL, Wu JB. Momordica charantia extract on insulin resistance and the skeletal muscle GLUT4 protein in fructose-fed rats. J Ethnopharmacol. 2009 May 4;123:82-90. 75. Sasa M, Inoue I, Shinoda Y, Takahashi S, Seo M, Komoda T, Awata T, Katayama S. Activating effect of momordin, extract of bitter melon (Momordica Charantia L.), on the promoter of human PPARdelta. J Atheroscler Thromb. 2009;16:888-92. 76. Fernandes NP, Lagishetty CV, Panda VS, Naik SR. An experimental evaluation of the antidiabetic and antilipidemic properties of a standardized Momordica charantia fruit extract. BMC Complement Altern Med. 2007;7:29. 77. Sarkar S, Pranava M, Marita R. Demonstration of the hypoglycemic action of Momordica charantia in a validated animal model of diabetes. Pharmacol Res. 1996 Jan;33:1-4. 78. Chan LL, Chen Q, Go AG, Lam EK, Li ET. Reduced adiposity in bitter melon (Momordica charantia)-fed rats is associated with increased lipid oxidative enzyme activities and uncoupling protein expression. J Nutr. 2005 Nov;135:2517-23. 79. Harinantenaina L, Tanaka M, Takaoka S, Oda M, Mogami O, Uchida M, Asakawa Y. Momordica charantia constituents and antidiabetic screening of the isolated major compounds. Chem Pharm Bull (Tokyo). 2006 Jul;54:1017-21. 80. Virdi J, Sivakami S, Shahani S, Suthar AC, Banavalikar MM, Biyani MK. Antihyperglycemic effects of three extracts from Momordica charantia. J Ethnopharmacol. 2003 Sep;88:107-11. 81. Roffey BW, Atwal AS, Johns T, Kubow S. Water extracts from Momordica charantia increase glucose uptake and adiponectin secretion in 3T3-L1 adipose cells. J Ethnopharmacol. 2007 May 30;112:77-84. 82. Ojewole JA, Adewole SO, Olayiwola G. Hypoglycaemic and hypotensive effects of Momordica charantia Linn (Cucurbitaceae) whole-plant aqueous extract in rats. Cardiovasc J S Afr. 2006/11/23 ed; 2006. p. 227-32. 83. Oishi Y, Sakamoto T, Udagawa H, Taniguchi H, Kobayashi-Hattori K, Ozawa Y, Takita T. Inhibition of increases in blood glucose and serum neutral fat by Momordica charantia saponin fraction. Biosci Biotechnol Biochem. 2007 Mar;71:735-40. 84. Yibchok-anun S, Adisakwattana S, Yao CY, Sangvanich P, Roengsumran S, Hsu WH. Slow acting protein extract from fruit pulp of Momordica charantia with insulin secretagogue and insulinomimetic activities. Biol Pharm Bull. 2006 Jun;29:1126-31. 85. Khanna P, Jain SC, Panagariya A, Dixit VP. Hypoglycemic activity of polypeptide-p from a plant source. J Nat Prod. 1981 Nov-Dec;44:648-55. 86. Ng TB, Wong CM, Li WW, Yeung HW. Insulin-like molecules in Momordica charantia seeds. J Ethnopharmacol. 1986 Jan;15:107-17. 87. Nerurkar PV, Lee YK, Linden EH, Lim S, Pearson L, Frank J, Nerurkar VR. Lipid lowering effects of Momordica charantia (Bitter Melon) in HIV-1-protease inhibitor-treated human hepatoma cells, HepG2. Br J Pharmacol. 2006 Aug;148:1156-64. 88. Nerurkar PV, Lee YK, Nerurkar VR. Momordica charantia (bitter melon) inhibits primary human adipocyte differentiation by modulating adipogenic genes. BMC Complement Altern Med. 2010;10:34. 89. Popovich DG, Lee Y, Li L, Zhang W. Momordica charantia seed extract reduces pre-adipocyte viability, affects lactate dehydrogenase release, and lipid accumulation in 3T3-L1 cells. J Med Food. 2011 Mar;14:201-8. 90. Chen Q, Li ET. Reduced adiposity in bitter melon (Momordica charantia) fed rats is associated with lower tissue triglyceride and higher plasma catecholamines. Br J Nutr. 2005 May;93:747-54. 91. Chen PH, Chen GC, Yang MF, Hsieh CH, Chuang SH, Yang HL, Kuo YH, Chyuan JH, Chao PM. Bitter melon seed oil-attenuated body fat accumulation in diet-induced obese mice is associated with cAMP-dependent protein kinase activation and cell death in white adipose tissue. J Nutr. 2012 Jul;142:1197-204. 92. Huang HL, Hong YW, Wong YH, Chen YN, Chyuan JH, Huang CJ, Chao PM. Bitter melon (Momordica charantia L.) inhibits adipocyte hypertrophy and down regulates lipogenic gene expression in adipose tissue of diet-induced obese rats. Br J Nutr. 2008 Feb;99:230-9. 93. Sekar, D.S., K. Sivagnanam, and S. Subramanian, Antidiabetic activity of Momordica charantia seeds on streptozotocin induced diabetic rats. Pharmazie, 2005. 60(5): p. 383-7. 94. Ahmed, I., et al., Beneficial effects and mechanism of action of Momordica charantia juice in the treatment of streptozotocin-induced diabetes mellitus in rat. Mol Cell Biochem, 2004. 261(1-2): p. 63-70. 95. Kumar Shetty, A., G. Suresh Kumar, and P. Veerayya Salimath, Bitter gourd (Momordica charantia) modulates activities of intestinal and renal disaccharidases in streptozotocin-induced diabetic rats. Mol Nutr Food Res, 2005. 49(8): p. 791-6. 96. Miura, T., et al., Hypoglycemic activity of the fruit of the Momordica charantia in type 2 diabetic mice. J Nutr Sci Vitaminol (Tokyo), 2001. 47(5): p. 340-4. 97. Grover, J.K., S.S. Rathi, and V. Vats, Amelioration of experimental diabetic neuropathy and gastropathy in rats following oral administration of plant (Eugenia jambolana, Mucuna pruriens and Tinospora cordifolia) extracts. Indian J Exp Biol, 2002. 40(3): p. 273-6. 98. Chuang, C.Y., et al., Fractionation and identification of 9c, 11t, 13t-conjugated linolenic acid as an activator of PPARalpha in bitter gourd (Momordica charantia L.). J Biomed Sci, 2006. 13(6): p. 763-72. 99. Kaku, K., et al., Genetic analysis of glucose tolerance in inbred mouse strains. Evidence for polygenic control. Diabetes, 1988. 37(6): p. 707-13. 100. Kooptiwut, S., et al., Comparison of insulin secretory function in two mouse models with different susceptibility to beta-cell failure. Endocrinology, 2002. 143(6): p. 2085-92. 101. Toye, A.A., et al., A genetic and physiological study of impaired glucose homeostasis control in C57BL/6J mice. Diabetologia, 2005. 48(4): p. 675-86. 102. Rossmeisl, M., et al., Variation in type 2 diabetes--related traits in mouse strains susceptible to diet-induced obesity. Diabetes, 2003. 52(8): p. 1958-66. 103. Kayo, T., et al., Identification of two chromosomal loci determining glucose intolerance in a C57BL/6 mouse strain. Comp Med, 2000. 50(3): p. 296-302. 104. Reeves, P.G., F.H. Nielsen, and G.C. Fahey, Jr., AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr, 1993. 123(11): p. 1939-51. 105. Shih, C.C., et al., Momordica charantia extract on insulin resistance and the skeletal muscle GLUT4 protein in fructose-fed rats. J Ethnopharmacol, 2009. 123(1): p. 82-90. 106. Spiegelman, B.M., P. Puigserver, and Z. Wu, Regulation of adipogenesis and energy balance by PPARgamma and PGC-1. Int J Obes Relat Metab Disord, 2000. 24 Suppl 4: p. S8-10. 107. Uldry, M., et al., Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation. Cell Metab, 2006. 3(5): p. 333-41. 108. Lin, J., et al., Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell, 2004. 119(1): p. 121-35. 109. Leone, T.C., et al., PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol, 2005. 3(4): p. e101. 110. Bostrom, P., et al., A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature, 2012. 481(7382): p. 463-8. 111. Wu, Z., et al., Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell, 1999. 98(1): p. 115-24. 112. Wenz, T., et al., Increased muscle PGC-1alpha expression protects from sarcopenia and metabolic disease during aging. Proc Natl Acad Sci U S A, 2009. 106(48): p. 20405-10. 113. Yang, X., S. Enerback, and U. Smith, Reduced expression of FOXC2 and brown adipogenic genes in human subjects with insulin resistance. Obes Res, 2003. 11(10): p. 1182-91. 114. Semple, R.K., et al., Expression of the thermogenic nuclear hormone receptor coactivator PGC-1alpha is reduced in the adipose tissue of morbidly obese subjects. Int J Obes Relat Metab Disord, 2004. 28(1): p. 176-9. 115. Tiraby, C., et al., Acquirement of brown fat cell features by human white adipocytes. J Biol Chem, 2003. 278(35): p. 33370-6. 116. Puigserver, P., et al., A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell, 1998. 92(6): p. 829-39. 117. Hansson, A., et al., A switch in metabolism precedes increased mitochondrial biogenesis in respiratory chain-deficient mouse hearts. Proc Natl Acad Sci U S A, 2004. 101(9): p. 3136-41. 118. Xia, Y., et al., Electrical stimulation of neonatal cardiomyocytes results in the sequential activation of nuclear genes governing mitochondrial proliferation and differentiation. Proc Natl Acad Sci U S A, 1997. 94(21): p. 11399-404. 119. Chan, L.L., et al., Reduced adiposity in bitter melon (Momordica charantia)-fed rats is associated with increased lipid oxidative enzyme activities and uncoupling protein expression. J Nutr, 2005. 135(11): p. 2517-23. 120. Cousin, B., et al., Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization. J Cell Sci, 1992. 103 ( Pt 4): p. 931-42. 121. Ghorbani, M. and J. Himms-Hagen, Appearance of brown adipocytes in white adipose tissue during CL 316,243-induced reversal of obesity and diabetes in Zucker fa/fa rats. Int J Obes Relat Metab Disord, 1997. 21(6): p. 465-75. 122. Barbatelli, G., et al., The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am J Physiol Endocrinol Metab, 2010. 298(6): p. E1244-53. 123. Fisher, F.M., et al., FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis. Genes Dev, 2012. 26(3): p. 271-81. 124. Sell, H., et al., Peroxisome proliferator-activated receptor gamma agonism increases the capacity for sympathetically mediated thermogenesis in lean and ob/ob mice. Endocrinology, 2004. 145(8): p. 3925-34. 125. Petrovic, N., et al., Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem, 2010. 285(10): p. 7153-64. 126. Chao, C.Y., M.C. Yin, and C.J. Huang, Wild bitter gourd extract up-regulates mRNA expression of PPARalpha, PPARgamma and their target genes in C57BL/6J mice. J Ethnopharmacol, 2011. 135(1): p. 156-61. 127. Sasa, M., et al., Activating effect of momordin, extract of bitter melon (Momordica Charantia L.), on the promoter of human PPARdelta. J Atheroscler Thromb, 2009. 16(6): p. 888-92. 128. Chen, P.H., et al., Bitter melon seed oil-attenuated body fat accumulation in diet-induced obese mice is associated with cAMP-dependent protein kinase activation and cell death in white adipose tissue. J Nutr, 2012. 142(7): p. 1197-204. 129.Chuang, C.Y., et al., Fractionation and identification of 9c, 11t, 13t-conjugated linolenic acid as an activator of PPARalpha in bitter gourd (Momordica charantia L.). J Biomed Sci, 2006. 13(6): p. 763-72. 130. Khanna, P., et al., Hypoglycemic activity of polypeptide-p from a plant source. J Nat Prod, 1981. 44(6): p. 648-55. 131. Tan, M.J., et al., Antidiabetic activities of triterpenoids isolated from bitter melon associated with activation of the AMPK pathway. Chem Biol, 2008. 15(3): p. 263-73. 132. Cheng, H.L., et al., A cell-based screening identifies compounds from the stem of Momordica charantia that overcome insulin resistance and activate AMP-activated protein kinase. J Agric Food Chem, 2008. 56(16): p. 6835-43. 133. Kuo, L.C., et al., Hydrolysis of black soybean isoflavone glycosides by Bacillus subtilis natto. Appl Microbiol Biotechnol, 2006. 73(2): p. 314-20. 134. Kuo, L.C. and K.T. Lee, Cloning, expression, and characterization of two beta-glucosidases from isoflavone glycoside-hydrolyzing Bacillus subtilis natto. J Agric Food Chem, 2008. 56(1): p. 119-25. 135. Kim, Y.W., et al., Metformin restores leptin sensitivity in high-fat-fed obese rats with leptin resistance. Diabetes, 2006. 55(3): p. 716-24. 136. Jiang, Z.Y., et al., Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA-mediated gene silencing. Proc Natl Acad Sci U S A, 2003. 100(13): p. 7569-74. 137. Winder, W.W., Energy-sensing and signaling by AMP-activated protein kinase in skeletal muscle. J Appl Physiol, 2001. 91(3): p. 1017-28. 138. 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, 1999. 87(5): p. 1990-5. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/62828 | - |
| dc.description.abstract | 糖尿病是血糖調節異常之代謝性疾病,其中90%均屬於第二型糖尿病 (Type 2 Diabetes Mellitus, T2DM) 。根據世界衛生組織統計T2DM罹患人口有逐年增加之趨勢。苦瓜 (Momordica charantia)為熱帶地區常見之蔬菜,也是一種傳統用於治療糖尿病之草藥。許多文獻指出苦瓜具降血糖功效。本研究之主要目的在探討山苦瓜血糖調節之活性萃物/區分物,以為發展保健食品之基礎。
研究材料為花蓮四號山苦瓜全果凍乾粉末(BGP),試驗模式則為餵食50%蔗糖飲食或30%高脂飲食之C57BL/6J公鼠,此品系具基因變異致胰島素分泌不足且易致胖。首先進行山苦瓜改善血糖調節之功效確認,結果顯示餵食5% BGP 22週後,顯著降低小鼠體重、體脂,並顯著改善禁食與餐後血糖、口服葡萄糖耐受性及胰島素耐受性,且有較低之HbA1c。進一步以水或乙酸乙酯萃取BGP,將所得之萃取物 (水萃物WE/乙酸乙酯萃物EAE) 或其殘渣餵食血糖偏高之C57BL6J公鼠,結果顯示水萃物具降血糖活性,乙酸乙酯萃物則否,且萃除EAE之殘渣仍有活性,但山苦瓜粉加熱後便失去血糖調節活性。進一步以3kDa 超微薄膜過濾法將WE進行區分為小分子 (WES) 和大分子 (WEL),並將WE以β-glucosidase水解再以乙酸乙酯萃取 (We-E)。以30% (w/w) 高脂飲食誘發C57BL/6J公鼠產生肥胖及高血糖症狀,供進行WE及其區分物之單劑量投予試驗,以評估WE及各種區分物血糖調節活性。結果顯示WE, WES, We-E於葡萄糖耐受性測試中均呈現血糖下降更快速之現象。而進一步每日管餵2100 mg/kgBW WE、1800 mg/kgBW WES或300 mg/kgBW WEL連續十週後,三者均改善OGTT,WE及WES亦顯著降低餐後血糖,顯著升高insulinogenic index,而WE具有增加肌肉及脂肪組織Akt磷酸化之傾向。 鑑於粒線體功能異常被認為在T2DM扮演重要角色,本研究進一步偵測組織中粒線體生成相關基因之表現。發現BGP促進:(1)副睪脂PPARγ及PGC1α、脂肪酸氧化基因 CPT1a, ACD1、UCP1及粒腺體生合成基因NrF1表現 (p<0.05); (2)棕脂PPARδ, PGC1α及NrF1表現; (3)腓腸肌PGC1α, ACS1及 tfam表現 (p<0.05)。且BGP增加小鼠黑暗期氧消耗量、二氧化碳排出量及呼吸商(RQ)值。顯示山苦瓜可促進熱量消耗。 綜之,山苦瓜水萃物對改善血糖調節具直接貢獻,其中以分子量小於3kD之區分物活性最高,但分子量大於3kD之區分物長期餵食亦有活性。而山苦瓜改善粒線體功能,對血糖調節之改善應亦有間接貢獻。顯示山苦瓜含有多種調節血糖之活性化合物,透過多種機制,改善血糖調節。 | zh_TW |
| dc.description.abstract | Diabetes Mellitus (DM) is a progressive metabolic disease primarily diagnosed based on impaired serum glucose control. Over 90% of DM patients are Type 2 (T2DM). According to WHO, prevalence of T2DM is increasing and of great public health concern. Bitter gourd ((Momordica charantia, BG) is a common tropical vegetable also used in traditional medicine, especially for treating diabetes. The hypoglycemic effect of various preparations of BG has been reported. This study examined BG and its extracts for the effect on glucose homeostasis control, aiming at providing the foundation for the development of functional food. Fresh Hualien No.4 wild bitter gourd whole fruit was lyophilized and grounded to obtain BGP. C57BL/6J mice fed a 50% sucrose diet or a high fat high sucrose diet served as the study model. Mice fed a 5% BGP diet showed a significantly lower fasting serum glucose and HbA1c, better glucose tolerance and insulin tolerance. Water extract (WE), ethyl acetate(EA) extract (EAE) and residues from EA extraction were then fed to mice. The results showed that WE but not EAE showed a hypoglycemic effect. Residues from EA extraction was also effective, but not heated BGP. The WE was then separated by an ultrafilration apparatus with a molecular cut-off of 3 kD to obtain fractions with molecular weight ≧3kD (WEL) or <3kD(WES). The WE was also treated with beta glucosidase and extracted with EA to obtain the We-E fraction. A single dose of WE, or the 3 fractions were gavaged to mice previously fed a 30% fat diet. OGTT or iPGTT were performed 30 min after the administration of WE or its fraction. Oral administration of WE, WES and We-E but not WEL resulted in significant improvement of glucose tolerance. Mice were respectively gavaged with 2100 mg/kgBW/day of WE、1800 mg/kgBW/day of WES or 300 mg/kgBW/day of WELfor 10 weeks. All three treatments improved OGTT. Feeding WE and WES also reduced postprandial serum glucose and increased insulinogenic index. WE also tended to increase Akt phosphorylation in muscle and white adipose tissue. As mitochondria dysfunction is considered to play an important role in the pathogenesis of T2DM, expressions of genes related to mitochondria biogenesis were examined in mice fed BGP or WE fractions. Mice fed BGP had lower body weight and adipose mass, higher mRNA of UCP1, PGC-1α and NrF1 in the white adipose tissue, PGC-1α and NrF1 or tfam in skeletal muscle and brown adipose tissue. These mice also had higher O2 consumption, CO2 production and respiratory quotient in the dark phase (p<0.05), indicating a higher energy expenditure.In conclusion, Water extract of BGP might directly regulate glucose homeostasis control. The small molecular weight fraction of WE (WES) has greater contribution, but WEL also has some effect after 10 weeks of feeding. An increased expenditure through enhancing mitochondria biogenesis and “browning” of white adipose, which resulted in less adipose accumulation. | en |
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| dc.description.tableofcontents | 總目錄
第一章、緒論-------------------------------------------------------------------------1 1.1 前言---------------------------------------------------------------------------------------------1 1.2 文獻回顧---------------------------------------------------------------------------------------5 1.2.1 胰島素分泌與腸泌素效應-------------------------------------------------------------5 1.2.2 胰島素訊息傳遞及缺損----------------------------------------------------------------6 1.2.3 胰島素阻抗-------------------------------------------------------------------------------8 1.2.4發炎介質與胰島素阻抗-----------------------------------------------------------------8 1.2.5脂質堆積與胰島素阻抗-----------------------------------------------------------------9 1.2.6 糖尿病小鼠模式C57BL/6J-----------------------------------------------------------10 1.2.7 苦瓜--------------------------------------------------------------------------------------11 1.2.7.1 簡介--------------------------------------------------------------------------------11 1.2.7.2 苦瓜調節血糖機制與有效成份-----------------------------------------------11 1.2.7.3 苦瓜調節體脂/血脂可能機制-------------------------------------------------12 1.3 實驗目的與架構-----------------------------------------------------------------------------25 第二章 山苦瓜改善血糖調節功能確認--------------------------------------27 2.1 前言與試驗大綱-----------------------------------------------------------------------------27 2.2 材料與方法-----------------------------------------------------------------------------------29 2.2.1 試驗大綱--------------------------------------------------------------------------------29 2.2.2 動物飼養--------------------------------------------------------------------------------30 2.2.3 飼料配製--------------------------------------------------------------------------------30 2.2.4 氧消耗量、二氧化碳排出量及呼吸商測定--------------------------------------31 2.2.5 口服葡萄糖耐受性測試--------------------------------------------------------------31 2.2.6 胰島素耐受性測試--------------------------------------------------------------------32 2.2.7 動物犧牲--------------------------------------------------------------------------------32 2.2.8 血液葡萄糖、三酸甘油酯、膽固醇、胰島素分析-----------------------------32 2.2.9 醣化血色素測定-----------------------------------------------------------------------34 2.2.10 Real-time PCR法分析基因表現----------------------------------------------------34 2.3 結果--------------------------------------------------------------------------------------------36 2.3.1終體重、體重變化量、攝食量、飼料及能量利用率----------------------------36 2.3.2 組織絕對及相對重量-----------------------------------------------------------------36 2.3.3 餵食實驗飼料前及第4, 9, 22週禁食血糖及16週飽食血糖濃度-----------36 2.3.4 氧消耗量、二氧化碳排出量及呼吸商--------------------------------------------37 2.3.5 口服葡萄糖耐受性測試--------------------------------------------------------------37 2.3.6 餵食實驗飼料16.5週後,胰島素耐受性測試血糖濃度----------------------37 2.3.7 禁食血清三酸甘油酯濃度及膽固醇濃度-----------------------------------------37 2.3.8 副睪白色脂肪、棕色脂肪、肌肉及肝臟mRNA表現-------------------------38 2.4 討論與結論-----------------------------------------------------------------------------------38 第三章 山苦瓜各種萃取物改善血糖調節之活性比較--------------------54 3.1 前言-------------------------------------------------------------------------------------------54 3.2 材料與方法----------------------------------------------------------------------------------55 3.2.1 試驗大綱--------------------------------------------------------------------------------55 3.2.2 山苦瓜全果凍乾粉末各種萃取物製備流程--------------------------------------56 3.2.3 管餵樣品配製--------------------------------------------------------------------------57 3.2.4 飼料配製--------------------------------------------------------------------------------57 3.2.5 動物飼養--------------------------------------------------------------------------------58 3.2.6 動物犧牲與樣品收集-----------------------------------------------------------------59 3.2.7 分析項目--------------------------------------------------------------------------------59 3.2.8 數據整理與統計分析-----------------------------------------------------------------59 3.3 結果-------------------------------------------------------------------------------------------59 3.3.1 終體重、體重增加量、攝食量及飼料利用率-----------------------------------59 3.3.2 組織器官絕對與相對重量-----------------------------------------------------------60 3.3.3 血液生化值-----------------------------------------------------------------------------60 3.3.4 統整表-----------------------------------------------------------------------------------60 3.4 討論與結論----------------------------------------------------------------------------------61 第四章 以單劑量投予試驗評估山苦瓜水萃物及其區分物之血糖調節活性----------------------------------------------------------------------------------70 4.1 前言-------------------------------------------------------------------------------------------70 4.2 實驗材料與方法----------------------------------------------------------------------------72 4.2.1 實驗大綱--------------------------------------------------------------------------------72 4.2.2 萃物製備--------------------------------------------------------------------------------73 4.2.3 管餵樣品配製與投予劑量-----------------------------------------------------------74 4.2.4 動物飼養--------------------------------------------------------------------------------75 4.2.5 葡萄糖耐受性測試--------------------------------------------------------------------76 4.2.6 血糖分析原理與方法-----------------------------------------------------------------76 4.2.7 統計分析--------------------------------------------------------------------------------76 4.3 結果-------------------------------------------------------------------------------------------76 4.3.1 山苦瓜水萃取物-----------------------------------------------------------------------76 4.3.2 山苦瓜水萃取物區分物-大、小分子----------------------------------------------76 4.3.3 山苦瓜水萃取區分物- P fraction----------------------------------------------------77 4.3.4 山苦瓜水萃取物區分物-酵素反應後之乙酸乙酯萃物-------------------------77 4.4 討論與結論----------------------------------------------------------------------------------77 第五章 以十週餵食試驗評估山苦瓜水萃取物及其區分物之血糖調節活性----------------------------------------------------------------------------------84 5.1 前言與試驗大鋼-----------------------------------------------------------------------------84 5.2 材料與方法-----------------------------------------------------------------------------------85 5.2.1 試驗大綱--------------------------------------------------------------------------------85 5.2.2 萃物製備與管餵劑量-----------------------------------------------------------------85 5.2.3 動物飼養--------------------------------------------------------------------------------85 5.2.4 飼料配製--------------------------------------------------------------------------------87 5.2.5 口服葡萄糖耐受性測試--------------------------------------------------------------87 5.2.6 血糖分析--------------------------------------------------------------------------------87 5.2.7 血清胰島素分析-----------------------------------------------------------------------88 5.2.8 胰島素耐受性測試--------------------------------------------------------------------88 5.2.9 動物犧牲--------------------------------------------------------------------------------88 5.2.10 血液三酸甘油酯、膽固醇分析----------------------------------------------------88 5.2.11 肝脂分析-------------------------------------------------------------------------------88 5.2.12 組織Akt磷酸化分析----------------------------------------------------------------90 5.2.13 基因表現-------------------------------------------------------------------------------94 5.2.14 統計分析-------------------------------------------------------------------------------95 5.3 結果--------------------------------------------------------------------------------------------95 5.3.1 終體重、體重變化量、攝食及能量利用率---------------------------------------95 5.3.2 絕對與相對組織重量-----------------------------------------------------------------95 5.3.3 空腹和進食後血清葡萄糖濃度及血清和肝臟三酸甘油酯與膽固醇濃度--95 5.3.4 口服葡萄糖耐受性測試血糖濃度與曲線下面積--------------------------------96 5.3.5 胰島素耐受性測試--------------------------------------------------------------------96 5.3.6 肝臟、腓腸肌及副睪白色脂肪組織Akt磷酸化分析--------------------------96 5.3.7 肝臟、腹部白色及棕色脂肪組織mRNA表現量-------------------------------97 5.4 綜合討論與結論-----------------------------------------------------------------------------97 第六章 綜合討論與總結-------------------------------------------------------118 圖目錄 第一章 圖1-1 The natural history of type 2 diabetes---------------------------------------------------3 圖1-2 餵食C57BL/6J公鼠含1% (w/w) 山苦瓜凍乾粉末之試驗飲食六週後口服葡萄糖耐受性測試-----------------------------------------------------------------------------------5 圖1-3 Prandial insulin and glucose excursions in healthy individuals emphasizing the very early, nervous system driven, insulin spike (cephalic phase) so important for rapid and effective inhibition of hepatic glucose output and NEFA efflux, and glucose disposal----------------------------------------------------------------------------------------------6 圖1-4葡萄糖刺激胰臟β細胞胰島素分泌機制--------------------------------------------7 圖1-5 regulation of IR: involved mediators and pathways----------------------------------8 第二章 圖2-1 body weight and serum glucose concentration after feeding AIN-76 modified basal diet containing 50% (w/w) sucrose for indicated weeks------------------------------28 圖2-2餵食C57BL/6J 公鼠實驗飼料16週後,隔夜禁食再餵食5小時之攝食量與血漿葡萄糖濃度----------------------------------------------------------------------------------45 圖2-3餵食C57BL/6J 公鼠實驗飼料4及22週後血液 (A) 三酸甘油酯及 (B)膽固醇濃度 --------------------------------------------------------------------------------------------46 圖2-4餵食C57BL/6J 公鼠實驗飼料5週後,(A) 每克體重氧氣消耗量與 (B) 曲線下面積 --------------------------------------------------------------------------------------------47 圖2-5餵食C57BL/6J 公鼠實驗飼料5週後,(A) 每克體重二氧化碳消耗量與 (B) 曲線下面積 --------------------------------------------------------------------------------------48 圖2-6餵食C57BL/6J 公鼠實驗飼料5週後,(A) 呼吸商數 (Respiratory Quotient; RQ) 與 (B) 曲線下面積 ----------------------------------------------------------------------49 圖2-7餵食C57BL/6J 公鼠實驗飼料9週後口服葡萄糖耐受性測試血液之 (A) 葡萄糖濃度與曲線下面積 (B) 胰島素濃度與曲線下面積-------------------------------50 圖2-8餵食C57BL/6J 公鼠實驗飼料16.5週後腹腔注射胰島素耐受性測試 (A) 血液之葡萄糖濃度與曲線下面積 (AUC) (B) 相對血糖濃度與曲線下面積 (AUC)--51 圖2-9餵食C57BL/6J 公鼠實驗飼料22週後 (A) 副睪白色脂肪組織與 (B) 棕色脂肪組織基因表現----------------------------------------------------------------------------------52 圖2-10餵食C57BL/6J 公鼠實驗飼料22週後 (A) 腓腸肌與 (B) 肝臟基因表現 -------------------------------------------------------------------------------------------------------53 第三章 圖3-1山苦瓜各種萃取物製備流程-----------------------------------------------------------57 圖3-2餵食C57BL/6J公鼠實驗飼料兩週後之終體重、體重增加量及食物攝取量-------------------------------------------------------------------------------------------------------62 圖3-3餵食C57BL/6J公鼠實驗飼料兩週後之血液 (A)葡萄糖 (B) 三酸甘油酯及(C) 膽固醇濃度----------------------------------------------------------------------------------------67 圖3-4餵食C57BL/6J公鼠實驗飼料兩週後之血液 (A)胰島素 (B) 胰島素抗性指標-------------------------------------------------------------------------------------------------------68 第四章 圖4-1 (A) Chemical structures of cucurbitane triterpenoids from bitter melon. Effect of Cucurbitane Triterpenoids on GLUT4 Translocation in (B) L6 myotubes (C) 3T3-L1. -------------------------------------------------------------------------------------------------------73 圖4-2 山苦瓜水萃物及其區分物製備流程-------------------------------------------------80 圖4-3 口服山苦瓜水萃取物對於 (A) 口服葡萄糖耐受性測試 (B) 腹腔注射葡萄糖耐受性測試之C57BL/6J公鼠血漿葡萄糖濃度變化量之影響------------------------81 圖4-4口服山苦瓜水萃取物小分子區分物 (WES) 對於 (A) 腹腔注射葡萄糖耐受性測試 (B) 單獨管餵WES之C57BL/6J公鼠血漿葡萄糖濃度變化量之影響-------82 圖4-5口服山苦瓜水萃取物大分子區分物 (WEL) 對於 (A) 腹腔注射葡萄糖耐受性測試 (B) 單獨管餵WEL之C57BL/6J公鼠血漿葡萄糖濃度變化量之影響------83 圖4-6單一劑量 (A) 口服或 (B) 腹腔注射山苦瓜水萃取物P fraction C57BL/6J公鼠血漿葡萄糖濃度變化量之影響-------------------------------------------------------------84 圖4-7口服山苦瓜水萃物酵素水解之乙酸乙酯萃物 (We-E) 及未經酵素水解之乙酸乙酯萃物 (Wne-E) 對於腹腔注射葡萄糖耐受性測試之C57BL/6J公鼠血漿葡萄糖濃度變化量之影響----------------------------------------------------------------------------85 第五章 圖5-1餵食C57BL/6J 公鼠實驗飼料八週之進食五小時後血清葡萄糖濃度-------109 圖5-2餵食C57BL/6J公鼠實驗飼料5週後口服葡萄糖耐受性試驗之 (A) 血清葡萄糖與曲線下面積 (B) 胰島素與曲線下面積----------------------------------------------110 圖5-3餵食C57BL/6J公鼠實驗飼料5週後口服葡萄糖耐受性試驗之 (A) 胰島素抗性指標HOMA-IR index (B) 第15分鐘之insulinogenic index--------------------------111 圖5-4 餵食C57BL/6J公鼠實驗飼料8週後胰島素耐受性試驗之 (A) 血清葡萄糖濃度 (B) 曲線下面積-------------------------------------------------------------------------112 圖5-5餵食C57BL/6J公鼠實驗飼料10週後肝臟、腓腸肌及腹部白色脂肪組織總Akt、磷酸化Akt及Akt磷酸化比例-------------------------------------------------------113 圖5-6餵食C57BL/6J公鼠實驗飼料10週後肝臟基因表現----------------------------114 圖5-7餵食C57BL/6J公鼠實驗飼料10週後副睪白色脂肪組織基因表現-----------115 圖5-8餵食C57BL/6J公鼠實驗飼料10週後棕色脂肪組織基因表現-----------------116 表目錄 第一章 表1-1 目前治療第二型糖尿病常用之口服/注射降血糖藥物優、缺點------------------1 表1-2 The mechanism of insulin resistance---------------------------------------------------14 表1-3 The possible hypoglycemia mechanism of bitter melon-----------------------------16 表1-4 The active hypoglycemia crude extract/compounds from bitter melon------------18 表1-5 The possible mechanism of bitter melon to decrease lipids in blood and tissue--21 第二章 表2-1、花蓮四號山苦瓜全果凍乾粉末長期餵食試驗飼料配方-------------------------31 表2-2、餵食C57BL/6J公鼠實驗飼料22週之終體重、體重變化量、攝食量、飼料及能量利用率-------------------------------------------------------------------------------------41 表2-3、餵食C57BL/6J公鼠實驗飼料22週後之肝臟、副睪及腹部白色脂肪、棕色脂肪絕對與相對重量----------------------------------------------------------------------------42 表2-4、餵食C57BL/6J公鼠實驗飼料22週後之器官絕對及相對重量--------------43 表2-5、餵食C57BL/6J公鼠實驗飼料前、4、9及22週後禁食血清葡萄糖及22週後糖化血色素百分比----------------------------------------------------------------------------44 第三章 表3-1、含花蓮四號山苦瓜全果凍乾粉末之試驗飼料配方-----------------------------58 表3-2、餵食C57BL/6J公鼠實驗飼料兩週後肝臟及脂肪器官絕對重量------------63 表3-3、餵食C57BL/6J公鼠實驗飼料兩週後肝臟及脂肪之器官相對重量---------64 表3-4、餵食C57BL/6J公鼠實驗飼料兩週後之器官絕對重量------------------------65 表3-5、餵食C57BL/6J公鼠實驗飼料兩週後之器官相對重量------------------------65 第四章 表4-1 各測試樣品中葡萄糖含量、管餵劑量、相對應樣品之Vehicle組管餵葡萄糖水劑------------------------------------------------------------------------------------------------71 表4-2 單一劑量投予降血糖活性試驗之小鼠飼料配方----------------------------------72 第五章 表5-1 花蓮四號山苦瓜水萃物,大、小分子區分物長期餵食試驗飼料配方----------87 表5-2、餵食C57BL/6J公鼠實驗飼料10週之終體重、體重變化量、攝食量、飼料及能量利用率-----------------------------------------------------------------------------------102 表5-3、餵食C57BL/6J公鼠實驗飼料10週後之肝臟及脂肪絕對重量----------------103 表5-4、餵食C57BL/6J公鼠實驗飼料10週後之肝臟及脂肪相對重量----------------104 表5-5、餵食C57BL/6J公鼠實驗飼料10週後之器官絕對重量-------------------------105 表5-6、餵食C57BL/6J公鼠實驗飼料10週後之器官相對重量-------------------------106 表5-7、餵食C57BL/6J公鼠實驗飼料前、3、5及10週後空腹血液葡萄糖濃度--107 表5-8、餵食C57BL/6J 公鼠實驗飼料10週後肝臟及肌肉三酸甘油酯及膽固醇濃度--------------------------------------------------------------------------------------------------108 | |
| dc.language.iso | zh-TW | |
| dc.subject | 粒線體 | zh_TW |
| dc.subject | 水萃物 | zh_TW |
| dc.subject | 血糖調節 | zh_TW |
| dc.subject | 山苦瓜 | zh_TW |
| dc.subject | mitochondria | en |
| dc.subject | water extract | en |
| dc.subject | blood glucose homeostasis | en |
| dc.subject | bitter melon | en |
| dc.title | 以C57BL/6J小鼠模式研發血糖恆定調節之山苦瓜萃物 | zh_TW |
| dc.title | Research and development of wild bitter melon extract for glucose homeostasis control using C57BL/6J mice as model | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-1 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 謝博軒,趙蓓敏,呂紹俊,楊偉勛,林璧鳳 | |
| dc.subject.keyword | 山苦瓜,血糖調節,水萃物,粒線體, | zh_TW |
| dc.subject.keyword | bitter melon,water extract,blood glucose homeostasis,mitochondria, | en |
| dc.relation.page | 134 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2013-02-18 | |
| 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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