簡易檢索 / 詳目顯示

研究生: 楊恆叡
論文名稱: 沒食子酸(gallic acid)對高果糖飼料誘導高血糖大鼠血糖及脂質代謝之影響
Effect of gallic acid on hyperglycemia and lipid metabolism in high fructose diet-induced diabetic rats
指導教授: 沈賜川
Shen, Szu-Chuan
學位類別: 碩士
Master
系所名稱: 人類發展與家庭學系
Department of Human Development and Family Studies
論文出版年: 2013
畢業學年度: 102
語文別: 中文
論文頁數: 83
中文關鍵詞: 沒食子酸糖尿病胰島素訊息傳遞胰島素阻抗高血糖
英文關鍵詞: diabetic rats, gallic acid, hypoglycemia, insulin signaling, lipid metabolism
論文種類: 學術論文
相關次數: 點閱:121下載:9
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 高血糖症(hyperglycemia)為糖尿病(diabetes mellitus )主要病徵,常伴隨胰島素阻抗(insulin resistance),使肝臟、肌肉、脂肪等週邊組織對於胰島素敏感性(insulin sensitivity)降低,影響血糖利用,導致人體長期對於葡萄糖耐受性不良。沒食子酸(gallic acid)為苯甲酸(benzoic acid)的衍生物,化學名3,4,5-trihydroxybenzoic acid,廣泛存在於各類植物中。近期研究發現酚酸類化合物具有抗氧化及改善葡萄糖攝入(glucose uptake)之功效。本研究探討沒食子酸對高果糖飼料誘導高血糖大鼠降血糖及脂質代謝之影響。餵食66%高果糖飼料12週後之Wistar大鼠分為四組(每組6隻),分別為:高果糖組、臨床糖尿病用藥(pioglitazone hydrochloride)組、低劑量(10 mg/kg B.W.)沒食子酸組、高劑量(30 mg/kg B.W.)沒食子酸組,糖尿病用藥與沒食子酸每日管餵一次,並與控制組(正常大鼠)作比較。老鼠於實驗進行17週後犧牲,結果顯示,糖尿病大鼠餵食30 mg/kg B.W.沒食子酸4週後,相較於高果糖組有明顯降低禁食血糖(fasting glucose) (從224.17 mg/dL降至84.83 mg/dL)及降低高胰島素血症 (從0.99 μg/L降低至0.42 μg/L)的效果;體脂肪方面,採集腎周脂肪(perirenal fat)及副睪脂肪(epididymal fat)進行分析,高劑量gallic acid組相較於高果糖組,明顯降低腎周脂肪(從6.7 mg降低至5.58 mg) 及副睪脂肪(從2.95 mg降低至2.02 mg);於脂肪組織中胰島素訊息傳遞方面,以西方墨點法偵測蛋白質表現量,結果顯示,餵食高劑量沒食子酸組相較於高果糖組可提昇54%葡萄糖轉運蛋白(glucosetransporter-4, GLUT4)表現量。综合以上結果推論,沒食子酸對於高果糖誘導高血糖大鼠具有降低血糖及調控脂質代謝之效果。

    Hyperglycemia is a major symptom of diabetes mellitus. It often associated with insulin resistance which will lower the insulin sensitivity of liver, muscles and adipose, futher effect the assimilation of blood sugar and lead to long-term impaired glucose tolerance (IGT). Gallic acid is the derivatives of benzoic acid (formula: 3,4,5 -trihydroxybenzoic acid) exists in various kinds of plants. Recent researches demonstrated that phenoic compounds exhibit anti-oxidation and improve glucose uptake activities in vitro. This study investigated the effect of gallic acid on hypoglycemia and lipid metabolism in high-fructose diet (HFD)-induced diabetic rats. After fed the 66% fructose for twelve weeks, the Wistar rats were devided into 4 groups (6 rats each group): HFD, pioglitazone hydrochloride, low dose (10 mg/kg B.W.) gallic acid, high dose (30 mg/kg B.W.) gallic acid groups. Rats fed the pioglitazone hydrochloride and the high dose (30 mg/kg B.W.) gallic acid once a day and were sacrified after experimenting for 17 weeks. The the fasting glucose and insulin levels of HFD rats significantly reduced (the former declined from 224.17 mg/dL to 84.83mg/dL, the latter declined from 0.99 μg/L to 0.42 μg/L) after a 4-week feeding of gallic acid (30 mg/kg B.W.). The perirenal and epididymal fats of the high dose gallic acid group significantly decreased compared to the HFD rats (the former declined from from 6.7 mg to 5.58 mg, the latter declined from 2.95 mg to 2.02 mg). The western blot analysis was conducted to evaluate the effect of gallic acid on insulin signal transduction pathway in adipose tissue of HFD rats. The high dose gallic acid increased 54% glucose transporter-4 (GLUT4) compared with the HFD rats. We postulate that gallic acid may alleviate hyperglycemia and modulate lipid metabolism of adipose in HFD rats.

    中文摘要………………………………………………………………………………2 英文摘要………………………………………………………………………………3 目錄……………………………………………………………………………………5 圖次……………………………………………………………………………………9 表次…………………………………………………………………………………..10 第一章 前言……………………….………………………………………………...12 第二章 文獻回顧……………………………………………………………………13 2.1酚酸………………………………………………………………………………13 2.1.1酚酸簡介……………………………………………………………………….13 2.1.2酚酸種類……………………………………………………………………….13 2.1.3酚酸與糖尿病………………………………………………………………….13 2.2糖尿病……………………………………………………………………………14 2.2.1糖尿病定義…………………………………………………………………….14 2.2.2糖尿病分類…………………………………………………………………….14 2.2.3糖尿病診斷標準…………………………………………………………… …16 2.2.4糖尿病流行病學……………………………………………………………….16 2.3胰島素阻抗………………………………………………………………………17 2.3.1胰島素簡介…………………………………………………………………….17 2.3.2 PI3K(Phosphatidylinositol-3-kinase)pathway…………………………………18 2.3.3葡萄糖轉運蛋白……………………………………………………………….20 2.3.5高果糖與胰島素阻抗………………………………………………………….23 2.3.6脂肪組織與胰島素阻抗……………………………………………………….25 2.4參與醣類代謝與脂質代謝之關鍵酵素…………………………………………29 2.4.1 Glycolysis pathway…………………………………………………………….29 2.4.2 De novo lipogenesis pathway…………………………………………………..29 2.4.3 Lipolysis pathway…………………………………………………………….. 31 2.5樣品與抗糖尿病藥物……………………………………………………………35 2.5.1沒食子酸……………………………………………………………………….35 2.5.2愛妥糖………………………………………………………………………….35 第三章 實驗架構……………………………………………………………………37 第四章 材料與方法…………………………………………………………………38 4.1實驗材料…………………………………………………………………………38 4.1.1實驗樣品來源………………………………………………………………….38 4.1.2實驗動物……………………………………………………………………….38 4.1.3動物飼料……………………………………………………………………….38 4.1.4實驗藥品與試劑……………………………………………………………….38 4.1.4.1化學藥品……………………………………………………………………..38 4.1.4.2酵素套組……………………………………………………………………..39 4.1.4.3抗體…………………………………………………………………………..40 4.1.4.4儀器設備……………………………………………………………………..40 4.2實驗方法…………………………………………………………………………41 4.2.1動物飼養……………………………………………………………………….41 4.2.2動物分組與誘導……………………………………………………………….41 4.2.3樣品餵食劑量………………………………………………………………….42 4.2.4口服葡萄糖耐受性試驗……………………………………………………….42 4.2.5血液的收集與處理…………………………………………………………….42 4.2.6臟器的採集…………………………………………………………………….42 4.2.7血漿葡萄糖濃度測定………………………………………………………….42 4.2.8血漿胰島素濃度測定………………………………………………………….43 4.2.9脂質代謝相關訊息傳遞蛋白測定………………………………………….....43 4.3 統計分析………………………………………………………………………...47 第五章 結果…………………………………………………………………………48 5.1灌食沒食子酸4週後大鼠進行口服葡萄糖耐受性試驗血漿葡萄糖濃度之變化……………..………………………………………………………………………48 5.2灌食沒食子酸4週後大鼠於禁食情況下血漿中葡萄糖濃度之變化…..……...48 5.3灌食沒食子酸4週後大鼠於禁食情況下血漿中果糖胺濃度之變化…..……..48 5.4灌食沒食子酸4週後大鼠於禁食情況下血漿中胰島素濃度之變化…..……...48 5.5灌食沒食子酸4週後大鼠於禁食情況下血漿中C胜鏈濃度之變化…..……..48 5.6灌食沒食子酸4週後大鼠體內脂肪組織堆積之變化…………………..……..49 5.7灌食沒食子酸4週後大鼠於禁食情況下血漿中三酸甘油酯濃度之變化……49 5.8灌食沒食子酸4週後大鼠於禁食情況下血漿中游離脂肪酸濃度之變化……49 5.9灌食沒食子酸4週後大鼠於禁食情況下血漿中高密度脂蛋白濃度之變化…49 5.10灌食沒食子酸4週後對大鼠腎周脂肪Glut4蛋白表現量之影響……………49 5.11灌食沒食子酸4週後對大鼠腎周脂肪IR蛋白表現量之影響………………..50 5.12灌食沒食子酸4週後對大鼠腎周脂肪PKC-ζ蛋白表現量之影響…………..50 5.13灌食沒食子酸4週後對大鼠腎周脂肪PFK蛋白表現量之影響…………….50 5.14灌食沒食子酸4週後對大鼠腎周脂肪PK蛋白表現量之影響……………...50 5.15灌食沒食子酸4週後對大鼠腎周脂肪FAS蛋白表現量之影響…………….50 5.16灌食沒食子酸4週後對大鼠腎周脂肪ATGL蛋白表現量之影響…………..51 第六章 討論…………………………………………………………………………52 6.1高果糖動物模式…………………………………………………………………52 6.2灌食沒食子酸對高果糖誘導高血糖大鼠高血糖症之影響……………………52 6.3灌食沒食子酸對高果糖誘導高血糖大鼠高胰島素血症之影響………………52 6.4灌食沒食子酸對高果糖誘導高血糖大鼠高血脂症之影響……………………53 6.5灌食沒食子酸對高果糖誘導高血糖大鼠內臟脂肪堆積之影響………………53 6.6灌食沒食子酸對高果糖誘導高血糖大鼠腎周脂肪胰島素訊息傳遞之影響…54 6.7灌食沒食子酸對高果糖誘導高血糖大鼠腎周脂肪糖解代謝之影響…………55 6.8灌食沒食子酸對高果糖誘導高血糖大鼠腎周脂肪脂質代謝之影響………….56 第七章 結論…………………………………………………………………………58 參考文獻……………………………………………………………………………..76

    中華民國糖尿病衛教學會。2010。糖尿病衛教核心教材。
    中華民國藥師公會藥學雜誌。2011。106:110-11
    王錫崗。2008。人體生理學。pp. 655-668。
    李天瑞。2008。數種食材萃物對脂肪或肌肉細胞葡萄糖攝取之影響。國立台灣大學。生命科學院微生物與生化學研究所。碩士論文。
    行政院衛生署。2012。行政院衛生署衛生統計資訊網。http://www.doh.gov.tw
    李雅婷。2004。酚酸衍生物之合成及其生物活性之研究。國立陽明大學。藥理學研究所。博士論文。
    吳寧容。2007。番石榴葉萃出物對streptozotocin-nicotinamide誘發第二型糖尿大白鼠血糖之影響。國立台灣大學。食品科技研究所。碩士論文。
    孫慧芸。2007。龍眼花水萃物對高果糖誘發代謝症候群大鼠之影響。國立台灣大學。食品科技研究所。碩士論文。
    黃士懿。2005a。營養生化學。pp.4.1-8。
    黃士懿。2005b。營養生化學。pp.6.1-52。
    張文昌。2010。食用桃金孃科植物萃取物減輕小鼠肝臟細胞(FL83B)胰島素阻抗之探討。國立台灣大學。食品科技研究所。碩士論文。
    Ahmed, I., Adeghate, E., Cummings, E., Sharma, A.K., and Singh, J. (2004). Beneficial effects and mechanism of action of Momordica charantia juice in the treatment of streptozotocin-induced diabetes mellitus in rat. Mol Cell Biochem 261, 63-70.
    Bhattacharya, S., Dey, D., and Roy, S.S. (2007). Molecular mechanism of insulin resistance. J Biosci 32, 405-413.
    Birnbaum, M.J. 2001. Turning down insulin signaling. J Clin Invest 108: 655-659.
    Brasaemle, D.L. (2010). Lipolysis Control: The Plot Thickens. Cell Metabolism 3, 173-174.
    Bryant, N.J., Govers, R., and James, D.E. (2002). Regulated transport of the glucose transporter GLUT4. Nat Rev Mol Cell Biol 3, 267-277.
    Calderhead, D.M., Kitagawa, K., Tanner, L.I., Holman, G.D., and Lienhard, G.E. (1990). Insulin regulation of th e two glucose transporters in 3T3-L1 adipocytes. J Biol Chem 265, 13801-13808.
    Chavez, J.A., and Summers, S.A. (2003). Characterizing the effects of saturated fatty acids on insulin signaling and ceramide and diacylglycerol accumulation in 3T3-L1 adipocytes and C2C12 myotubes. Arch Biochem Biophys 419, 101-109.
    Chirala, S.S., Jayakumar, A., Gu, Z.W., and Wakil, S.J.(2000). Human fatty acid synthase: Role of interdomain in the formation of catalytically active synthase dimer. PNAS 98, 3104–3108
    Ciaraldi, T., and Henry, R.R. (1997). Thiazolidinediones and their effects on glucose transporters. Eur J Endocrinol 137, 610-612.
    Claus, T.H., Lowe, D.B., Liang, Y., Salhanick, A.I., Lubeski, C.K., Yang , L.L., Lemoine , L.L., Zhu , J., Clairmont, K.B. (2005). Specific Inhibition of Hormone-Sensitive Lipase Improves Lipid Profile while Reducing Plasma Glucose. JPET 315:1396–1402.
    Czech, M.P., and Corvera, S. (1999). Signaling mechanisms that regulate glucose transport. J Biol Chem 274, 1865-1868.
    Day, C., Cartwright, T., Provost, J., and Bailey, C.J. (1990). Hypoglycaemic effect of Momordica charantia extracts. Planta Med 56, 426-429.
    DeFronzo, R.A., and Ferrannini, E. (1991). Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes care 14, 173-194.
    Delarue, J., and Magnan, C. (2007). Free fatty acids and insulin resistance. Curr Opin Clin Nutr Metab Care 10, 142-148.
    Dey, D., Basu, D., Roy, S.S., Bandyopadhyay, A., and Bhattacharya, S. (2006). Involvement of novel PKC isoforms in FFA induced defects in insulin signaling. Mol Cell Endocrinol 246, 60-64.
    Dresner, A., Laurent, D., Marcucci, M., Griffin, M.E., Dufour, S., Cline, G.W., Slezak, L.A., Andersen, D.K., Hundal, R.S., Rothman, D.L., et al. (1999). Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. J Clin Invest 103, 253-259.
    El-Kebbi, I.M., Roser, S., and Pollet, R.J. (1994). Regulation of glucose transport by pioglitazone in cultured muscle cells. Metabolism 43, 953-958.
    Erkelens, D.W. (2001). Insulin resistance syndrome and type 2 diabetes mellitus. Am J Cardiol 88, 38J-42.
    Eriksson, J.W. (2007). Metabolic stress in insulin’s target cells leads to ROS accumulation –A hypothetical common pathway causing insulin resistance. FEBS Letters 581, 3734–3742.
    J. Fanelli, C., Calderone, S., Epifano, L., De Vincenzo, A., Modarelli, F., Pampanelli, S., Perriello, G., De Feo, P., Brunetti, P., Gerich, J.E., et al. (1993). Demonstration of a critical role for free fatty acids in mediating counterregulatory stimulation of gluconeogenesis and suppression of glucose utilization in humans. J Clin Invest 92, 1617-1622
    Faure P, Rossini E, Lafond JL, Richard MJ, Favier A, Halimi S. 1997. Vitamin E improves the free radical defense system potential and insulin sensitivity of rats fed high fructose diets. J Nutr 127(1):103-107.
    Fievet, C., Fruchart, J.C., and Staels, B. (2006). PPARalpha and PPARgamma dual agonists for the treatment of type 2 diabetes and the metabolic syndrome. Curr Opin Pharmacol 6, 606-614.
    Funaki, M., Randhawa, P., and Janmey, P.A. (2004). Separation of insulin signaling into distinct GLUT4 translocation and activation steps. Mol Cell Biol 24, 7567-7577.
    Gao, X., Li, B., Jiang, H., Liu, F., Xu, D., and Liu, Z. (2007). Dioscorea opposita reverses dexamethasone induced insulin resistance. Fitoterapia 78, 12-15.
    Gesta, S., Bluher, M., Yamamoto, Y., Norris, A.W., Berndt, J., Kralisch, S., Boucher, J., Lewis, C. and Kahn, C.R. (2006) Evidence for a role of developmental genes in the origin of obesity and body fat distribution . Proc Natl Acad Sci 103: 6676-6681.
    Goossens, G.H. (2008). The role of adipose tissue dysfunction in the pathogenesis of obesity-related insulin resistance. Physiol Behav 94, 206-218.
    Govers, R., Coster, A.C., and James, D.E. (2004). Insulin increases cell surface GLUT4 levels by dose dependently discharging GLUT4 into a cell surface recycling pathway. Mol Cell Biol 24, 6456-6466.
    Hajduch, E.J., Guerre-Millo, M.C., Hainault, I.A., Guichard, C.M., and Lavau, M.M. (1992). Expression of glucose transporters (GLUT 1 and GLUT 4) in primary cultured rat adipocytes: differential evolution with time and chronic insulin effect. J Cell Biochem 49, 251-258.
    Hoehn, K.L., Hohnen-Behrens, C., Cederberg, A., Wu, L.E., Turner, N., Yuasa, T., Ebina, Y., and James, D.E. (2008). IRS1-independent defects define major nodes of insulin resistance. Cell Metab 7, 421-433.
    Hsu, J.H., Wu, Y.C., Liu, I. M. and Cheng, J. T. (2007). Dioscorea as the principal herb of Die-Huang-Wan, a widely used herbal mixture in China, for improvement of insulin resistance in fructose-rich chow-fed rats. J Ethnopharmacol 112, 577-584.
    Huang, H.L., Hong, Y.W., Wong, Y.H., Chen, Y.N., Chyuan, J.H., Huang, C.J., and Chao, P.M. (2008). 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 99, 230-239.
    Huang, S., and Czech, M.P. (2007). The GLUT4 glucose transporter. Cell Metab 5, 237-252.
    Hwei, W.P., Tsai, M.J., Hsu, C.Y., Wang, C.Y., Hsu, H.K., Weng, C.F.(2007). Toona sinensis Roem (Meliaceae) leaf extract alleviates hyperglycemia via altering adipose glucose transporter 4.Food Chem Toxicol 7,2554-2560.
    Iwu, M.M., Okunji, C.O., Ohiaeri, G.O., Akah, P., Corley, D., and Tempesta, M.S. (1990). Hypoglycaemic activity of dioscoretine from tubers of Dioscorea dumetorum in normal and alloxan diabetic rabbits. Planta Med 56, 264-267.
    Jakus, V., Sapak, M., Kostolanska, J.(2012)Circulating TGF-β1, Glycation, and Oxidation in Children with Diabetes Mellitus Type 1.Exp Diabetes Res,1-7
    Jellinger, P.S., Mace, M.D.(2007). Metabolic Consequences of Hyperglycemia and Insulin Resistance. Clinical Cornerstone [Suppl 7]:S30–S42.
    Jeon, J.R., Lee, J.S., Lee, C.H., Kim, J.Y., Kim, S.D., and Nam, D.H. (2006). Effect of ethanol extract of dried Chinese yam (Dioscorea batatas) flour containing dioscin on gastrointestinal function in rat model. Arch Pharm Res 29, 348-353.
    Johnson, R.J., Perez-Pozo, S.E., Sautin, Y.Y., Manitius, J., Sanchez-Lozada, L.G., Feig, D.I., Shafiu, M., Segal, M., Glassock, R.J., Shimada, M., Roncal, C., and Nakagawa, T.(2009). Hypothesis: Could Excessive Fructose Intake and Uric Acid Cause Type 2 Diabetes? Endocrine Reviews 30(1):96–116.
    Jove, M., Planavila, A., Laguna, J.C., and Vazquez-Carrera, M. (2005). Palmitate-induced interleukin 6 production is mediated by protein kinase C and nuclear-factor kappaB activation and leads to glucose transporter 4 down-regulation in skeletal muscle cells. Endocrinology 146, 3087-3095.
    Kennedy, A., Martinez, K., Chuang, C.C., LaPoint, K., and McIntosh, M. (2009). Saturated fatty acid-mediated inflammation and insulin resistance in adipose tissue: mechanisms of action and implications. J Nutr 139, 1-4.
    Khanna, P., Jain, S.C., Panagariya, A., and Dixit, V.P. (1981). Hypoglycemic activity of polypeptide-p from a plant source. J Nat Prod 44, 648-655.
    Kim, H., Haluzik, M., Asghar, Z., Yau, D., Joseph, J.W., Fernandez, A.M., Reitman, M.L., Yakar, S., Stannard, B., Heron-Milhavet, L., et al. (2003). Peroxisome proliferator-activated receptor-alpha agonist treatment in a transgenic model of type 2 diabetes reverses the lipotoxic state and improves glucose homeostasis. Diabetes 52, 1770-1778.
    Kumar, N., and Dey, C.S. (2002). Metformin enhances insulin signalling in insulin-dependent and-independent pathways in insulin resistant muscle cells. Br J Pharmacol 137, 329-336.
    Kumar, N., and Dey, C.S. (2003). Development of insulin resistance and reversal by thiazolidinediones in C2C12 skeletal muscle cells. Biochem Pharmacol 65, 249-257. Lawson, M.A., and Purslow, P.P. (2000). Differentiation of myoblasts in serum-free media: effects of modified media are cell line-specific. Cells Tissues Organs 167, 130-137.
    Lee, C.C., Hsu, .W.H., Shen, S.R., Cheng, Y.H., Wu, .S.C.(2012). Fagopyrum tataricum (Buckwheat) Improved High-Glucose-Induced Insulin Resistance in Mouse Hepatocytes and Diabetes in Fructose-Rich Diet-Induced Mice.10, Exp Diabetes Res 375673-375683.
    Lewis, G.F., Vranic, M., Harley, P., and Giacca, A. (1997). Fatty acids mediate the acute extrahepatic effects of insulin on hepatic glucose production in humans. Diabetes 46, 1111-1119.
    Liao, W., Nguyen, M.T., Imamura, T., Singer, O., Verma, I.M., and Olefsky, J.M. (2006). Lentiviral short hairpin ribonucleic acid-mediated knockdown of GLUT4 in 3T3-L1 adipocytes. Endocrinology 147, 2245-2252.
    Langin, D. (2006). Control of fatty acid and glycerol release in adipose tissue lipolysis. Biologies 329 , 598–607
    Liao, W., Nguyen, M.T., Yoshizaki, T., Favelyukis, S., Patsouris, D., Imamura, T., Verma, I.M., and Olefsky, J.M. (2007). Suppression of PPAR-gamma attenuates insulin-stimulated glucose uptake by affecting both GLUT1 and GLUT4 in 3T3-L1 adipocytes. Am J Physiol Endocrinol Metab 293, E219-227.
    Liou, S.S., Liu, I.M., Hsu, S.F., and Cheng, J.T. (2004). Corni fructus as the major herb of Die-Huang-Wan for lowering plasma glucose in Wistar rats. J Pharm Pharmacol 56, 1443-1447.
    Long, S.D., and Pekala P.H. (1996). Regulation of GLUT4 gene expression by arachidonic acid. J biol Chem 271, 1138-1144.
    Lowell, B.B., and Shulman, G.I. (2005). Mitochondrial dysfunction and type 2 diabetes. Science 307, 384-387.
    Maury , E., and Brichard , S.M. (2010). Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Molecular and Cellular Endocrinology 314, 1–16.
    Marshall, S. (2006). Role of insulin, adipocyte hormones, and nutrient-sensing pathways in regulating fuel metabolism and energy homeostasis: a nutritional perspective of diabetes, obesity, and cancer. Issue 346, p. re7
    McAnuff, M.A., Harding, W.W., Omoruyi, F.O., Jacobs, H., Morrison, E.Y., and Asemota, H.N. (2005a). Hypoglycemic effects of steroidal sapogenins isolated from Jamaican bitter yam, Dioscorea polygonoides. Food Chem Toxicol 43, 1667-1672.
    Mei, J., Wang, C.N., O''Brien, L., and Brindley, D.N. (2003). Cell-permeable ceramides increase basal glucose incorporation into triacylglycerols but decrease the stimulation by insulin in 3T3-L1 adipocytes. Int J Obes Relat Metab Disord 27, 31-39.
    Michelle Furtado, L., Poon, V., and Klip, A. (2003). GLUT4 activation: thoughts on possible mechanisms. Acta Physiol Scand 178, 287-296.
    Minokoshi, Y., Kahn, C.R., and Kahn, B.B. (2003). Tissue-specific ablation of the GLUT4 glucose transporter or the insulin receptor challenges assumptions about insulin action and glucose homeostasis. J Biol Chem 278, 33609-33612.
    Moller, D.E. (2001). New drug targets for type 2 diabetes and the metabolic syndrome. Nature 414, 821-827.
    Ng, T.B., Li, W.W., and Yeung, H.W. (1989). Effects of lectins with various carbohydrate binding specificities on lipid metabolism in isolated rat and hamster adipocytes. Int J Biochem 21, 149-155.
    Ng, T.B., Wong, C.M., Li, W.W., and Yeung, H.W. (1987a). Acid-ethanol extractable compounds from fruits and seeds of the bitter gourd Momordica charantia: effects on lipid metabolism in isolated rat adipocytes. Am J Chin Med 15, 31-42.
    Nishiumi, S., and Ashida, H. (2007). Rapid preparation of a plasma membrane fraction from adipocytes and muscle cells: application to detection of translocated glucose transporter 4 on the plasma membrane. Biosci Biotechnol Biochem 71, 2343-2346.
    Nugent, C., Prins, J.B., Whitehead, J. P., Savage, D., Wentworth, J.M., Chatterjee, V.K., and O’Rahilly S. (2001). Potentiation of glucose uptake in 3T3-L1 adipocytes by PPARγ agonists is maintained in cells expressing a PPARγ dominant-negative mutant: evidence for selectivity in the downstream responsis to PPARγ activation. Mol Endocrinol 15, 1729-1738
    Oka, Y., Asano, T., Shibasaki, Y., Kasuga, M., Kanazawa, Y., and Takaku, F. (1988). Studies with antipeptide antibody suggest the presence of at least two types of glucose transporter in rat brain and adipocyte. J Biol Chem 263, 13432-13439.
    Parks, W.C., Darke, R.L.(1982).Insulin mediates the stimulation of pyruvate kinase by a dual mechanism. Biochem. J. 208, 333-337.
    Petersen, K.F., and Shulman, G.I. (2006). Etiology of insulin resistance. Am J Med 119, S10-16.
    Platel, K., and Srinivasan, K. (1997). Plant foods in the management of diabetes mellitus: vegetables as potential hypoglycaemic agents. Nahrung 41, 68-74.
    Rabe, K., Lehrke, M., Parhofer, K.G., and Broedl, U.C. (2008). Adipokines and insulin resistance. Mol Med 14, 741-751.
    Reaven, G.M. (1988). Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37, 1595-1607.
    Reaven, G.M. (2008). Insulin resistance: the link between obesity and cardiovascular disease. Endocrinol Metab Clin North Am 37, 581-601, vii-viii.
    Roffey, B.W., Atwal, A.S., Johns, T., and Kubow, S. (2007). Water extracts from Momordica charantia increase glucose uptake and adiponectin secretion in 3T3-L1 adipose cells. J Ethnopharmacol 112, 77-84.
    Prasad, C.N.V., Anjana, T., Banerji, A., Gopalakrishnapillai, A.(2010)Gallic acid induces GLUT4 translocation and glucose uptake activity in 3T3-L1 cells. FEBS Letters 584, 531–536
    Punithavathi, V. R., Prince, P.S.M., Kumar, M.R., Selvakumari, C.J.(2011). Protective Effects of Gallic Acid on Hepatic Lipid Peroxide Metabolism, Glycoprotein Components and Lipids in Streptozotocin-Induced Type II Diabetic Wistar Rats. J Biochem Mol Toxicol 2, 68-76.
    Sakoda, H., Ogihara, T., Anai, M., Funaki, M., Inukai, K., Katagiri, H., Fukushima, Y., Onishi, Y., Ono, H., Fujishiro, M., et al. (2000). Dexamethasone-induced insulin resistance in 3T3-L1 adipocytes is due to inhibition of glucose transport rather than insulin signal transduction. Diabetes 49, 1700-1708.
    Saltiel, A.R., and Olefsky, J.M. (1996). Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes 45, 1661-1669.
    Schmitz-Peiffer, C., Craig, D.L., and Biden, T.J. (1999). Ceramide generation is sufficient to account for the inhibition of the insulin-stimulated PKB pathway in C2C12 skeletal muscle cells pretreated with palmitate. J Biol Chem 274, 24202-24210.
    Silva, A.P.P., Alves, G.G., Araujo, A.H.B., SOLA-PENNA, M.(2004). Effects of insulin and actin on phosphofructokinase activity and cellular distribution in skeletal muscle. Annals of the Brazilian Academy of Sciences 76, 541-548.
    Silva, D.D., Zancan, P., Coelho, W.C., Gomez, .L.S(2010)Metformin reverses hexokinase and 6-phosphofructo-1-kinase inhibition in skeletal muscle, liver and adipose tissues from streptozotocin-induced diabetic mouse. Archives of Biochemistry and Biophysics 496, 53–60.
    Semenkovich, C.F.(1997).Regulation of fatty acid synthase. Prog. Lipid Res. 36:43–53.
    Smith, U. (2002). Impaired (''diabetic'') insulin signaling and action occur in fat cells long before glucose intolerance--is insulin resistance initiated in the adipose tissue? Int J Obes Relat Metab Disord 26, 897-904.
    Spiegelman, B.M., and Flier, J.S. (1996). Adipogenesis and obesity: rounding out the big picture. Cell 87, 377-389.
    Stuart, C.A., Wen, G., Gustafson, W.C., and Thompson, E.A. (2000). Comparison of GLUT1, GLUT3, and GLUT4 mRNA and the subcellular distribution of their proteins in normal human muscle. Metabolism 49, 1604-1609.
    Stuart, C.A., Yin, D., Howell, M.E., Dykes, R.J., Laffan, J.J., and Ferrando, A.A. (2006). Hexose transporter mRNAs for GLUT4, GLUT5, and GLUT12 predominate in human muscle. Am J Physiol Endocrinol Metab 291, E1067-E1073.
    Tafuri, S.R. (1996). Troglitazone enhances differentiation, basal glucose uptake, and Glut1 protein levels in 3T3-L1 adipocytes. Endocrinology 137, 4706-4712.
    Thirone, A.C., Huang, C., and Klip, A. (2006). Tissue-specific roles of IRS proteins in insulin signaling and glucose transport. Trends Endocrinol Metab 17, 72-78.
    Tofade, T.S., and Liles, E.A. (2004). Intentional overdose with insulin glargine and insulin aspart. Pharmacotherapy 24, 1412-1418.
    Tschop, M., and Thomas, G. (2006). Fat fuels insulin resistance through Toll-like receptors. Nat Med 12, 1359-1361.
    Turnbow, M.A., Keller, S.R., Rice, K.M., and Garner, C.W. (1994). Dexamethasone down-regulation of insulin receptor substrate-1 in 3T3-L1 adipocytes. J Biol Chem 269, 2516-2520.
    Undie, A.S., and Akubue, P.I. (1986). Pharmacological evaluation of Dioscorea dumetorum tuber used in traditional antidiabetic therapy. J Ethnopharmacol 15, 133-144.
    Vague, J. (1956). The degree of masculine differentiation of obesities: a factor determining predisposition to diabetes, atherosclerosis, gout, and uric calculous disease. Am J Clin Nutr 4, 20-34.
    Van Epps-Fung, M., Williford, J., Wells, A., and Hardy, R.W. (1997). Fatty acid-induced insulin resistance in adipocytes. Endocrinology 138, 4338-4345.
    Wei, Y., Chen, K., Whaley-Connell, A.T., Stump, C.S., Ibdah, J.A., and Sowers, J.R. (2008). Skeletal muscle insulin resistance: role of inflammatory cytokines and reactive oxygen species. Am J Physiol Regul Integr Comp Physiol 294, R673-R680.
    White, M.F. (2002). IRS proteins and the common path to diabetes. Am J Physiol Endocrinol Metab 283, E413-E422.
    White, M.F., and Kahn, C.R. (1994). The insulin signaling system. J Biol Chem 269, 1-4.
    Wood, I.S., Hunter, L., and Trayhurn, P. (2003). Expression of Class III facilitative glucose transporter genes (GLUT-10 and GLUT-12) in mouse and human adipose tissues. Biochem Biophys Res Commun 308, 43-49.
    Wood, I.S., and Trayhurn, P. (2003). Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br J Nutr 89, 3-9.
    Wymann, M. P., and Schneiter, R. (2008). Lipid signalling in disease. Nat Rev Mol Cell Biol 9, 162-176.
    Yamada, K., Noguchi, T.(1999).Nutrient and hormonal regulation of pyruvate kinase gene expression .Biochem. J. 337 ,1-11.
    Yen, C.L., Farese, R.V.(2006). Fat breakdown: A function for CGI-58 (ABHD5) provides a new piece of the puzzle. Cell Metabolism 5 , 305-307.
    Zimmermann, R., Strauss, J.G., Haemmerle, G., Schoiswohl, G., Gruenberger, R.B., Riederer, M., Lass, A., Neuberger, .G., Eisenhaber, F., Hermetter, A., Zechner, R.(2004).Albin Hermetter,3Rudolf Zechner Fat Mobilization in Adipose Tissue Is Promoted by Adipose Triglyceride Lipase.Science 306,1383-1386.

    下載圖示
    QR CODE