跳到主要內容

臺灣博碩士論文加值系統

(44.213.60.33) 您好!臺灣時間:2024/07/21 13:40
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:黃大維
研究生(外文):Da-Wei Huang
論文名稱:咖啡酸及肉桂酸減輕小鼠肝臟細胞(FL83B)胰島素阻抗及改善碳水化合物代謝之研究
論文名稱(外文):Alleviation of Insulin Resistance and Improvement in Carbohydrate Metabolism in Insulin Resistant Mouse Liver FL83B Cells by Caffeic acid and Cinnamic acid
指導教授:吳瑞碧
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:食品科技研究所
學門:農業科學學門
學類:食品科學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:中文
論文頁數:105
中文關鍵詞:糖尿病咖啡酸肉桂酸葡萄糖攝入肝醣合成胰島素阻抗
外文關鍵詞:Diabetes mellituscaffeic acidcinnamic acidglucose uptakeglycogen synthesisinsulin resistance
相關次數:
  • 被引用被引用:5
  • 點閱點閱:1458
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:2
糖尿病為胰島素分泌缺乏或胰島素作用缺失所導致的一種醣類代謝的慢性疾病。約 95% 的糖尿病患者屬於第二型糖尿病,發生原因主要為胰島素作用缺失及體內細胞對胰島素無法引起正常之反應而導致高血糖症。咖啡酸及肉桂酸為多種水果、蔬菜及咖啡中常存在的兩種酚酸,近來已有許多研究在評估此兩酚酸抗高血糖之活性。
本實驗以 TNF-α 誘導小鼠肝臟 FL83B 細胞產生胰島素阻抗,再評估咖啡酸及肉桂酸之增加阻抗細胞葡萄糖攝入及改善醣類代謝。實驗中以葡萄糖攝入實驗評估兩種酚酸降血糖之效果,並分析胰島素訊息蛋白、肝醣合成相關酵素以及糖質新生酵素的表現,以解釋胰島素阻抗 FL83B 細胞中葡萄糖攝入增加與肝醣合成之改善。
於抗高血糖效果實驗中發現,咖啡酸及肉桂酸會促進胰島素受器 (Insulin receptor, IR) 磷酸化及增加胰島素訊息相關蛋白包括磷酸肌醇激酶(phosphatidylinositol-3 kinase, PI3K)、肝醣合成酶 (glycogen synthase, GS) 及葡萄糖轉運蛋白 (glucose transporter-2, GLUT-2) 的表現。於改善醣類代謝結果顯示,此兩種酚酸會增加胰島素阻抗細胞中葡萄糖激酶 (Glucokinase, GK),但會減少肝醣合成酶激酶 (glycogen synthase kinase, GSK)、肝醣合成酶 serine 磷酸、肝細胞核因子 (hepatic nuclear factor-4, HNF-4) 及磷酸烯醇式丙酮酸羧激酶(phosphoenolpyruvate carbooxykinase, PEPCK) 的表現。根據以上之結果推測,咖啡酸及肉桂酸可以藉由改善胰島素阻抗 FL83B 細胞對胰島素的敏感度而促進細胞葡萄糖攝入及改善醣類代謝。
Diabetes mellitus (DM) is a chronic disease associated with carbohydrate metabolism and caused by a deficiency in insulin secretion or by the ineffectiveness in insulin action. About 95% of the diabetic incidences belong to type 2 diabetes, of which the main cause of hyperglycemia is the ineffectiveness in insulin action or the inability to induce a normal response to insulin in the cells. Two phenolic acids, caffeic acid and cinnamic acid, are commonly present in fruits, vegetables, and coffee. Anti-hyperglycemic activity has become a focus in recent studies on these two phenolic acids.
The present study investigated the effect of the two phenolics on enhancing glucose uptake and ameliorating carbohydrate metabolism in TNF-α-induced insulin resistant mouse liver FL83B cells.The uptake test of 2-[1-14C ] deoxy-D-glucose in insulin resistant FL83B cells was performed to evaluate the hypoglycemic effect. The expressions of insulin signal proteins, glycogen synthesis associated enzymes and the enzymes of gluconeogenesis were analyzed to elucidate the enhancement on glucose uptake and the restoration on glycogen synthesis in insulin resistant FL83B cells by the phenolic acids..
In the results of antihyperglycemic effect, the two phenolic acids promote insulin receptor tyrosyl phosphorylation, up-regulat the expression of insulin signal associated proteins, including insulin receptor, phosphatidylinositol-3 kinase (PI3K), glycogen synthase (GS), and glucose transporter-2 (GLUT-2). The results of amelioration on carbohydrate metabolism revealed that the two phenolic acids increase the expression of Glucokinase (GK), while decrease the expression of glycogen synthase kinase (GSK), Ser-641 phosphorylation of GS, hepatic nuclear factor-4 (HNF-4), and phosphoenolpyruvate carbooxykinase (PEPCK) in the resistant cells.
In conclusion, we speculate that caffeic acid and cinnamic acid may improve glucose uptake and ameliorate carbohydrate metabolism by restoring isulin sensitivity in insulin resistant FL83B cells. These two phenolic acids may restore glycogen synthesis, promote glucose uptake into cells, inhibit gluconeogehesis to decrease glucose formation, and result in the alleviation of insulin resistance in cells as the consequence.
中文摘要 ..……………………………………………………………………I
英文摘要 ..……………………………………………………………………II
目錄 ..…………………………………………………………………….IV
圖次 ..…………………………………………………………………………VII
表次 ..…………………………………………………………………………VIII
緒論 ..……………………………………………………………………… 1
第一章 文獻回顧 ..…………………………………………………………….3
第ㄧ節 糖尿病 ……………………………………………………………3
一、糖尿病的流行病學 ..………………………………………………… 3
二、糖尿病簡介 ..………………………………………………………… 3
三、糖尿病分類 ..………………………………………………………… 4
第二節 胰島素 ..……………………………………………………………8
一、胰島素簡介 ..………………………………………………………… 8
二、胰島素的作用 ..……………………………………………………… 8
三、胰島素在細胞層次之作用 ..………………………………………… 10
四、胰島素的訊息傳遞 ..………………………………………………… 12
五、胰島素與糖類代謝 ..………………………………………………… 17
第三節 胰島素阻 ..…………………………………………………………. 19
一、胰島素阻抗之病因 ..………………………………………………… 19
二、胰島素阻抗性之定義 ..……………………………………………… 19
三、Tumor necrosis factor-α 與胰島素阻抗 ..…………………………...21
四、以細胞模式探討胰島素阻抗之研究 ..………………………………23
第四節 抗糖尿病物質 ..…………………………………………………….26
一、常見抗糖尿病藥物 ..…………………………………………………26
二、新上市之降血糖藥物 ..……………………………………………… 29
第五節 酚酸抗糖尿病之研究 .…………………………………………….31
一、酚酸之介紹 ..………………………………………………………… 31
二、酚酸抗糖尿病 ..……………………………………………………… 31
第二章 研究動機與實驗架構 ..……………………………………………….35
第三章 咖啡酸與肉桂酸促進葡萄糖攝入及機制之探討 ..………………….37
第一節 前言 .……………………………………………………………….37
第二節 實驗材料 ..…………………………………………………………. 38
ㄧ、實驗樣品來源 ..………………………………………………………38
二、實驗細胞 ..…………………………………………………………… 38
三、實驗藥品及試劑 ..…………………………………………………… 38

四、實驗藥品配製 ...……………………………………………………… 39
五、儀器設備 ..…………………………………………………………… 41
第三節 實驗方法 ..…………………………………………………………. 42
ㄧ、TNF-α 誘導FL83B細胞胰島素阻抗之評估 ..……………… 42
二、FL83B 細胞對葡萄糖之攝入作用 ..………………………… 42
三、西方轉印分析細胞處理及蛋白質萃取 ..…………………… 43
四、西方轉印分析 ..……………………………………………… 43
五、統計分析 ..………………………………………………… 46
第四節 結果與討論 ..…………………………………………. 47
ㄧ、TNF-α 誘導 FL83B 細胞胰島素阻抗 ..…………………… 47
二、酚酸對具胰島素阻抗 FL83B 細胞葡萄糖攝入之影響 ..… 48
三、高濃度咖啡酸及肉桂酸對具胰島素阻抗 FL83B 細胞葡萄糖攝入之影響 ..………………………………………………...48
四、低濃度咖啡酸及肉桂酸對具胰島素阻抗 FL83B 細胞葡萄糖攝入之影響 ..………………………………………………………… 49
五、咖啡酸及肉桂酸於胰島素阻抗 FL83B 細胞葡萄糖攝入之影響 ..
49
六、咖啡酸及肉桂酸於胰島素阻抗 FL83B 細胞胰島素訊息之影響 .. 51
(一) 胰島素受體表現及其酪胺酸磷酸化 ..………………… 51
(二) 磷酸肌醇激酶表現 ..……………………………………… 52
(三) 肝醣合成酶及葡萄糖轉運蛋白表現 ..…………………………53
第五節 結論 ..……………………………………………………… 55
第四章 咖啡酸與肉桂酸促進肝醣合成及改善醣類代謝之探討 ………… 68
第一節 前言 ..…………………………………………… 68
第二節 實驗材料 ..…………………………………………… 69
ㄧ、實驗樣品來源 ..………………………………………… 69
二、實驗細胞 ..……………………………………………… 69
三、實驗藥品及試劑 .…………………………………………… 69
四、實驗藥品配製 ..………………………………………… 70
五、儀器設備 ..………………………………………………… 70
第三節 實驗方法 ..……………………………………………. 71
ㄧ、FL83B細胞中肝醣含量之測定 .………………………… 71
二、西方轉印分析細胞處理及蛋白質萃取 ..………………… 71
三、西方轉印分析 ..…………………………………………… 72
四、FL83B細胞中phosphoenolpyruvate carboxylase 活性測定 ..…….. 72
五、統計分析 ..………………………………………………… 72
第四節 結果與討論 ..………………………………………… 73
一、咖啡酸及肉桂酸對胰島素阻抗 FL83B 細胞肝醣含量之影響 … 73
二、咖啡酸及肉桂酸對胰島素阻抗 FL83B 細胞葡萄糖激酶之影響 .. 74
三、咖啡酸及肉桂酸對胰島素阻抗 FL83B 細胞肝醣合成酶磷酸化之影響 ..………………………………………………………… 75
四、咖啡酸及肉桂酸對胰島素阻抗 FL83B 細胞肝醣合成酶激酶-3
之影響 ..………………………………………………………… 76
五、咖啡酸及肉桂酸對胰島素阻抗 FL83B 細胞醣質新生之影響…… 78
第五節 結論 ..………………………………………………… 81
第五章 總結 ..…………………………………………………………………… 91
參考文獻 ..……………………………………………………………………. 93



圖 次
圖 1-1、糖尿病的分類 ..……………………………………………………… 7
圖 1-2、胰島素調節之代謝作用 ...…………………………… 9
圖 1-3、肝臟及肌肉中肝醣代謝示意圖 ……………………... 11
圖 1-4、胰島素訊息傳遞示意圖 ..…………………………… 13
圖 1-5、肝臟葡萄糖代謝之調節 ..……………………… 18
圖 1-6、(a) 胰島素於正常狀態調節葡萄糖平衡之作用 (b) 胰島素阻抗狀態造成之現象…………………………20
圖 1-7、TNF-α 減少 IRS-1 serine phosphorylation 的可能原因 ..…….22
圖 1-8、Hydroxybenzoic acid 及 Hydroxycinnamic acid 之化學結構 ……. 33
圖 1-9、綠原酸及咖啡酸之化學結構 ……………………. 34
圖 2-1、實驗架構 …………………………………………… 36
圖 3-1、TNF-α 抑制小鼠肝臟 FL83B 細胞葡萄糖攝入 ……… 56
圖 3-2、不同酚酸 (50 μM) 對具胰島素阻抗 FL83B 細胞葡萄糖攝入之影響 …………………………………………………. 57
圖 3-3、高濃度之咖啡酸對具胰島素阻抗 FL83B 細胞葡萄糖攝入之影響 58
圖 3-4、高濃度之肉桂酸對具胰島素阻抗 FL83B 細胞葡萄糖攝入之影響 59
圖 3-5、低濃度之咖啡酸對具胰島素阻抗 FL83B 細胞葡萄糖攝入之影響 60
圖 3-6、低濃度之肉桂酸對具胰島素阻抗 FL83B 細胞葡萄糖攝入之影響 61
圖 3-7、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞葡萄糖攝入之影響 …………………………………………...…62
圖 3-8、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞胰島素受器表現之影響 ……………………………………………… 63
圖 3-9、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞胰島素受器磷酸化之影響 …………………………………………. 64
圖 3-10、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞 PI3K 表現之影響 ………………………………………………. 65
圖 3-11、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞肝醣合成酶表現之影響 …………………………………………… 66
圖 3-12、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞葡萄糖轉運蛋白表現之影響……………………………………………67
圖 4-1、肝醣含量之標準曲線 …………………………………… 82
圖 4-2、FL83B細胞於不同處理下肝醣之含量 ………………….83
圖 4-3、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞葡萄糖激酶表現之影響 ……………………………………………… 84
圖 4-4、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞肝醣合成酶表現之影響 ……………………………………………… 85
圖 4-5、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞肝醣合成酶 serine 磷酸化之影響 ………………………………… 86.
圖 4-6、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞 glycogen synthase kinase-3α 之影響 ………………………… 87
圖 4-7、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞 glycogen synthase kinase-3β 之影響 ………………………… 88
圖 4-8、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞 hepatic nuclear factor-4 之影響……………………………… 89.
圖 4-9、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞 phosphoenolpyruvate carboxylase 之影響 ………………………90
圖 5-1、咖啡酸及肉桂酸減緩 FL83B 細胞胰島素阻抗可能之機制 ...…………………………………………… 92

表 次
表 1-1、輔助性葡萄糖轉運蛋白種類 ……………………… 16
何橈通。糖尿病與公共衛生。臨床醫學。1986。17: 300-317。
沈德昌、顏兆熊。第2型糖尿病藥物治療新知。台灣醫界。2005。466-471。
吳寧榮。2007。番石榴萃出物對streptozotocin-nicotinamide 誘發第二型糖尿病 大白鼠血醣之影響。國立台灣大學食品科技研究所碩士論文。
林進丁。胰島素。藥學雜誌。1986。2: 57-63。
許振耀。食療與健康。1993。錦明印刷有限公司。台北。
陳佩芬。人蔘皂苷 Rh2 降血糖機轉之研究。國立成功大學藥理學研究所碩士論 文。
鄭澄意。老化伴生脂質代謝異常之研究。1992。國防醫學院醫學科學研究所博士論文。
鄭芳琪。2009。番石榴葉水萃物降血糖作用及有效成分分離。國立台灣大學食品科技研究所博士論文。
潘長玉、尹士男。胰島素抵抗二型糖尿病發病機制的重要因素。2000。中華內分泌代謝雜誌,16: 56-57
Adisakwattana, S.; Moonsan, P.; Yibchok-Anun, S. Insulin-releasing properties of a series of cinnamic acid derivatives in vitro and in vivo. J. Agric. Food Chem. 2008, 56, 7838-7844.
Alastair J. J. Metformin. New Engl. J. Med. 1996, 334, 574-579.
American Diabetes Association: Standards of medical care in diabetes-2008. Diabetes Care 2008, 1, S12-S54.
American Diabetes Association. Diagnosis and classification of diabetes. Diabetes Care 2008, 31, S55-S60.
Andrew, W. J.; Vasquez, B.; Nagulesparan, M.; Klimes, I.; Foley, J.; Unger, R.; Reaven, G. M. Insulin therapy in obese non-insulin-independent diabetes induces improvement in insulin action and secretion that are maintained for two weeks after insulin withdrawal. Diabetes 1984, 30, 634-642.
Azuma, K.; Ippoushi, K.; Nakayama, M.; Ito, H.; Higashio, H.; Terao, J. Absorption of chlorogenic acid and caffeic acid in rats after oral administration. J. Agric. Food Chem. 2000, 48, 5496-5500.
Balasubashini, M. S.; Rukkumani, R.; Menon, V. P. Protective effects of ferulic acid on hyperlipidemic diabetic rats. Acta. Diabetol. 2003, 40, 118-122.
Baldwin, S. A. Mammalian passive glucose transporters: members of a ubiquitous family of active and passive transport proteins. Biochim. Biophys. Acta. 1993, 1154, 17-49.
Bergman, R. N.; Ader, M. Free fatty acids and pathogenesis of type 2 diabetes mellitus. Trends Endocrinol. Metab. 2000, 1, 351-356.
Bjőrnholm, M.; Zierath, J. R. Insulin signal transduction in human skeletal muscle: identifying the defects in type II diabetes. Biochem. Soc. Trans. 2005, 33, 354-357.
Bouskila, M.; Hirshman, M. F.; Jensen, J.; Goodyear, L. J.; Sakamoto, K. Insulin promotes glycogen synthesis in the absence of GSK3 phosphorylation in skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 2008, 294, E28-E35.
Brady, M. J.; Nairn, A. C.; Saltiel, A. R. The regulation of glycogen synthase by protein phosphatase 1 in 3T3-L1 adipocytes. Evidence for a potential role for DARPP-32 in insulin action. J. Biol. Chem. 1997, 272, 29698-29703.
Breslow, J. L.; Sloan, H. R.; Ferrans, V. J.; Anderson, J. L.; Levy, R. I. Characterization of the mouse liver cell line FL83B. Exp. Cell Res. 1973, 78, 441-453.
Butler, A. A.; LeRoith, D. Tissue-specific versus generalized gene targeting of the igf1 and igf1r genes and their roles in insulin-like growth factor physiology. Endocrinology 2001, 142, 1685-1688.
Byrne, C. D. Does tumour necrosis factor alpha influence insulin sensitivity in skeletal muscle. Clin Sci (Lond). 2000, 99, 329-330.
Cantley, L. C. The phosphoinositide 3-kinase pathway. Science 2002, 296, 1655-1657.
Cichy, S. B.; Uddin, S.; Danilkovich, A.; Guo, S.; Klippel, A.; Unterman, T. G. Protein kinase B/Akt mediates effect of insulin on hepatic insulin-like growth factor-binding protein-1 gene expression through a conserved insulin response sequence. J. Biol. Chem. 1998, 273, 6482-6487.
Cheng, J. T.; Liu, I. M. Stimulatory effect of caffeic acid on α1A-adrenoceptors to increase glucose uptake into cultured C2C12 cells. Naunyn. Schmiedebergs. Arch. Pharmacol. 2000, 362, 122-127.
Cheng, H. L.; Huang, H. K.; Chang, C. I.; Tsai, C. P.; Chou, C. H. 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, 5835-6843.
Cheng, F. C.; Shen, S. C.; Wu, J. S. B. Effect of guava (Psidium guajava L.) leaf extract on glucose uptake in rat hepatocytes. J. Food Sci. 2009, 74, H132-H138.
Clifford, M. N. Chlorogenic acids and other cinnamates-nature, occurrence and dietary burden. J. Sci. Food Agric. 1999, 79, 362-372.
Cross, D. A.; Alessi, D. R.; Cohen, P.; Andjelkovich, M.; Hemmings, B. A. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 1995, 378, 785-789.
Cusi, K.; Maezono, K.; Osman, A.; Pendergrass, M.; Patti, M. E.; Pratipanawatr, T.; DeFronzo, R. A.; Kahn, C. R.; Mandarino, L. J. Insulin resistance differentially affects the PI3-kinase- and MAP kinase-mediated signaling in human muscle. J. Clin. Invest. 2000, 105, 311-320.
DeFronzo, R. A.; Jocot, E.; Jequier, E.; Maeder, E.; Wahren, J.; Felber, J. P. The effect of insulin on the disposal of intravenous glucose. Diabetes 1981, 30, 1000-1007.
DeFronzo, R. A.; Ferrannini, E. Insulin resistance:a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991, 14, 173-194.
Del Aguila, L. F.; Claffey, K. P.; Kirwan, J. P. TNF-α impairs insulin signaling and insulin stimulation of glucose uptake in C2C12 muscle cells. Am. Physiol. Soci. 1999, 276, E849-855.
Feinstein, R.; Kanety, H.; Papa, M. Z.; Lunenfeld, B.; Karasik, A. Tumor necrosis factor-alpha suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates. J. Biol. Chem. 1993, 268, 26055-26058.
Ferre, T.; Pujol, A.; Riu, E.; Bosch, F.; Valera, A. Correction of diabetic alterations by glucokinase. Proc. Natl. Acad. Sci. USA. 1996, 93, 7225-7230.
Ferrer, J. C.; Favre, C.; Gomis, R. R.; Fernandez-Novell, J. M.; Garica-Rocha, M.; de la Iglesia, N.; Cid, E.; Guinovart, J. J. Control of glycogen deposition. FEBS Letter. 2003, 546, 127-132.
Garrait, G.; Jarrige, J. F.; Blanquet, S.; Beyssac, E.; Cardot, J. M.; Alric, M. Gastrointestinal absorption and urinary excretion of transcinnamic and p-coumaric acids in rats. J. Agric. Food Chem. 2006, 54, 2944-2950.
Gerich, J. E. The genetic basis of type 2 diabetes mellitus: impaired insulin secretion versus impaired insulin sensitivity. Endocr. Rev. 1998, 19, 491-503.
González-Espinosa, C.; Romero-Ávila, M. T.; Mora-Rodríguez, D. M.; González-Espinosa, D.; García-Sáinz J. A. Molecular cloning and functional expression of the guinea pig α1A-adrenoceptor. Eur. J. Pharmacol. 2001, 42, 147-155.
Goda, T.; Yamada, K.; Sugiyama, M.; Moriuchi, S.; Hosoya, N. Effect of sucrose and acarbose feeding on the development of streptozotocin-induced diabetes in the rat. J. Nutri. Sci. Vita. 1982, 28, 41-56.
Greenway, C. S.; Storey, B. K. Seasonal change and prolonged anoxia affect the kinetic properties of phosphofructokinase and pyruvate in oysters. J. Comp. Physiol. 2000, 170, 285-293.
Halle, M.; Berg, A.; Northoff, H.; Keul, J. Importance of TNF-alpha and leptin in obesity and insulin resistance: a hypothesis on the impact of physical exercise. Exerc. Immunol. Rev. 1998, 4, 77-94.
Hashimoto, N.; Kido, Y.; Uchida, T.; Matsuda, T.; Suzuki, K.; Inoue, H.; Matsumoto, M.; Ogawa, W.; Maeda, S.; Fujihara, H. PKClambda regulates glucose-induced insulin secretion through modulationof gene expression in pancreatic beta cells. J. Clin. Invest. 2005, 115, 138-145.
Horn, C. G. V.; Ivester, P.; Cunningham, C. C. Chronic ethanol consumption and liver glycogen synthesis. Arch. Biochem. Biophys. 2001, 392, 145-152.
Hotamisligil, G.; Shargill, N. S.; Spiegelman, B. M. Adipose expression of tumor necrosis-alpha: direct role in obesity-linked insulin resistance. Science 1993, 259, 87-91.
Hotamisligil, G. S.; Spiegelman, B. M. Tumor necrosis factor alpha: a key component of the obesity-diabetes link. Diabetes 1994, 4, 1271-1278.
Hsu, H.; Shu, H. B.; Pan, M. G.; Goeddel, D. V. TRADD-TRAF2 and TRADDF-ADD interactions define two distinct TNF receptor 1 signaling transduction pathways. Cell 1996, 84, 299-308.
Hu, Z. W.; Shi, X. Y.; Lin, R. Z.; Hoffman, B. B. Contrasting Signaling pathways of α1A- and α1B-adrenergic receptor subtype activation of phosphatidylinositol 3-kinase and ras in transfected NIH3T3 cells. Mol. Endo. 1999, 13, 3-14.
Hummel, K. P.; Dickie, M. W.; Coleman, D. L. Diabetes, new mutation in the mouse. Science (Wash DC) 1966, 153, 1127-1128.
Iwata, M.; Haruta, T.; Usui, I.; Takata, Y.; Takano, A.; Uno, T.; Kawahara, J.; Ueno, E.; Sasaoka, T.; Ishibashi, O.; Kobayashi, M. Pioglitazone ameliorates tumor necrosis factor-α-induced insulin resistance by a mechanism independent of adipogenic activity of peroxisome proliferator-activated receptor-γ. Diabetes 2001, 50, 1083-1092.
Iynedjian, P. B.; Gjinovci, A.; Renold, A. E. Stimulation by insulin of glucokinase gene transcription in liver of diabetic rats. J. Biol. Chem. 1988, 263, 740-744.
James, D. E. The mammalian facilitative glucose transporter family. Int. Union Physiol. Sci. 1995, 10, 67-71.
Johnson, A. B.; Webster, J. M.; Sum, C. F.; Heseltine, L.; Argyraki, M.; Cooper, B.G. The impact of metformin therapy on hepatic glucose production and skeletal muscle glycogen synthase activity in overweight type 2 diabetic patients. Metabolism 1993, 42, 1217-1222.
Joost, H. G.; Bell, G. I.; Best, J. D.; Birnbaum, M. J.; Charron, M. J.; Chen, Y. T.; Doege, H.; James, D. E.; Lodish, H. F.; Moley, K. H. Nomenclature of the GLUT/SLC2A family of sugar/polyol transport facilitators. Am. J. Physiol. 2002, 282, E974-E976.
Jung, U. J.; Lee, M. K.; Park, Y. B.; Jeon, S. M.; Choi, M. S. Antihyperglycemic and antioxidant properties of caffeic acid in db/db mice. J. Pharmaco. Experi. Therap. 2006, 318, 476-483.
Kabayama, K.; Sato, T.; Kitamura, F.; Uemura, S.; Kang, B. W.; Igarashi, Y.; Inokuchi, J. TNF-α-induced in adipocytes as a memebrane michrodomain disorder: involvement of ganglioside GM3. Glycobiology 2005, 15, 21-29.
Keilson, L.; Mather, S.; Walter, Y. H. Synergistic effects of nategtlinide and meal administration on insulin secretion in patients with type 2 diabetic mellitus. J. Clin. Endocrinol. Metab. 2000, 85, 1081-1086.
Kroder, G.; Bossenmayer, B.; Kellerer, M.; Capp, E.; Stoyanov, B.; Muhlhofer, A.; Berti, L.; Horikoshi, H.; Ullrich, A.; Haring, H. Tumor necrosis factor-alpha and hyperglycemia-induced insulin resistance. J. Clin. Invest. 1996, 97, 1471-1477.
Kumar, N.; Dey, C. Development of insulin resistance and reversal by thiazolidinediones in C2C12 skeletal muscles. Biochem. Pharmacol. 2003, 65, 249-257.
Leclercq, I. A.; Morais, A. D. S.; Schroyen, B.; Hul, N. V.; Geerts, A. Insulin resistance in hepatocytes and sinusoidal liver cells: mechanisms and consequences. J. Hepatol. 2007, 47, 142-156.
Lietzke, S. E.; Bose, S.; Cronin, T.; Klarlund, J.; Chawla, A.; Czech, M. P.; Lambright, D. G. Structural basis of 3-phosphoinositide recognition by pleckstrin homology domains. Mol. Cell 2000, 6, 385-394.
Liu, I. M.; Hsu, F. L.; Chen, C. F.; Cheng, J. T. Antihyperglycemic action of isoferulic acid in streptozotocin-induced diabetic rats. Br. J. Pharmacol. 2000, 129, 631-636.
Liu, I. M.; Tsai, C. C.; Lai, T. Y.; Cheng, J. T. Stimulatory effect of isoferulic acid on α1A-adrenoceptor to increase glucose uptake into cultured myoblast C2C12 cell of mice. Autonomic Neurosci. Basic Clin. 2001, 88, 175-180.
Maier, V. H.; Gould, G. W. Long-term insulin treatment of 3T3-L1 adipocytes results in mis-targeting of GLUT4: implications for insulin-stimulated glucose transport. Diabetologia 2000, 43, 1273-1281.
Manach, C.; Scalbert, A.; Morand, C.; Rémésy, C.; Jiménez, L. Polyphenols: food sources and bioavailability. Am. J. Clin. Nutr. 2004, 79, 727-747.
McEvoy, G. K. AHFS drug information. American Society of Health-System Pharmacists 2000, 28, 2862-2864.
Mittelman, S. D.; Fu, Y. Y.; Rebrin, K.; Bergman, R. N. Indirect effect of insulin to suppress endogenous glucose production is dominant, even with hyperglucagonemia. Diabetes, Modified militaris (Linn.) Link Chem SOC. 2005, 2299-2300.
Moller, D. E. Potential role of TNF-alpha in the pathogenesis of insulin resistance and type 2 diabetes. Trends Endocrinol. Metab. 2000, 6, 212-217.
Moore, M. C.; Cherrington, A. D.; Wasserman, D. H. Regulation of hepatic and peripheral glucose disposal. Best Pract. Res. Clin. Endocrinol. Metab. 2003, 17, 343-364.
Mueckler, M. Facilitative glucose transporters. Eur. J. Biochem. 1994, 219, 713-725.
Mueckler, M. Introduction: Insulin-sensitive glucose transport. Cell Deveal. Biol. 1996, 7, 227-228.
Musi, N.; Hirshman, M. F.; Nygren, J.; Svanfeldt, M.; Bavenholm, P.; Rooyackers, O.; Zhou, G.; Williamson, J. M.; Ljunqvist, O.; Efendic, S.; Moller, DE.; Thorell, A.; Goodyear, L. J. Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes 2002, 51, 2074-2081.
Niehof, M.; Borlak J. HNF4α and the Ca-channel TRPC1 are novel disease candidate genes in diabetic nephropathy. Diabetes 2008, 57, 1069-1077.
Nikoulina, S. E.; Ciaraldi, T. P.; Mudaliar, S.; Mohideen, P.; Carter, L.; Henry, R. R. Potential role of glycogen synthase kinase-3 in skeletal muscle insulin resistance of Type 2 diabetes. Diabetes 2000, 49, 263-271.
Ohnishi, M.; Matuo, T.; Tsuno, T.; Hosoda, A.; Nomura, E.; Taniguchi, H.; Sasaki, H.; Morishita, H. Antioxidant activity and hypoglycemic effect of ferulic acid in STZ-induced diabetic mice and KK-Ay mice. Biofactors 2004, 21, 315-319.
Okada, T.; Kawano, Y.; Sakakibara, T.; Hazeki, O.; Ui, M. Essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes. Studies with a selective inhibitor wortmannin. J. Biol. Chem. 1994, 269, 3568-3573.
Okutan, H.; Ozcelikb, N.; Yilmazb, H. R.; Uzb, E. Effects of caffeic acid phenethyl ester on lipid peroxidation and antioxidant enzymes in diabetic rat heart. Clin. Biochem. 2005, 38, 191-196.
Oreña, S. J.; Torchia, A. J.; Garofalo, R. S. Inhibition of glycogen synthase kinase-3 (GSK3) stimulates glycogen synthase and glucose transport by distinct mechanisms in 3T3-L1 adipocytes. J. Biol. Chem. 2000, 275, 15765-15772.
Panunti, B.; Jawa, A. A.; Fonseca, V. A. Mechanisms and therapeutic targets in type 2 diabetes mellitus. Drug Discovery Today: Disease Mechanisms 2004, 1, 151-157.
Park, S. H.; Min, T. S. Caffeic acid phenethyl ester ameliorates changes in IGFs secretion and gene expression in streptozotocin-induced diabetic rats. Life Sci. 2006, 78, 1741-1747.
Peraldi, P.; Hotamisligil, G. S.; Buurman, W. A.; White, M. F.; Spiegelman, B. M. Tumor necrosis factor (TNF-α) inhibits insulin signaling through stimulation of the p55 TNF receptor and activation of sphingomyelinase. J. Biol. Chem. 1996, 271, 13018-13022.
Peradi, P.; Xu, M.; Spiegelman, B. M. Thiazolidinediones block tumor necrosis factor-α-induced inhibition of insulin singaling. J. Clin. Invest. 1997, 100, 1863-1869.
Pessin, J. E.; Bell, G. I. Mammalian facilitative glucose transporter family: Structure and molecular regulation. Annu. Rev. Physiol. 1992, 54, 911-930.
Pilkis, S. J.; Granner, D. K. Molecular physiology of the regulation of hepatic gluconeogenesis and glycolysis. Annu. Rev. Physiol. 1992, 54, 885-909.
Postic, C.; Shiota, M.; Niswender, K. D.; Jetton, T. L.; Chen, Y.; Moates, J. M.; Shelton, K. D.; Lindner, J.; Cherrington, A. D.; Magnuson, M. A. Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic β-cell-specific gene knock-outs using cre recombinase. J. Biol. Chem. 1999, 274, 305-315.
Radtke, J.; Linseisen, J.; Wolfram, G. Phenolic acid intake of adults in a Bavarian subgroup of the national food consumption survey. Z. Ernaehrungswiss 1998, 37, 190-197.
Rangwala, S. M.; Lazar, M. A. Peroxisome proliferators-activated receptor in diabetes and metabolism. Trend Pharmacol. Sci. 2004, 25, 331-336.
Reaven, G. M. Role of insulin resistance in human disease. Diabetes 1988, 37, 1595-1607.
Rechner, A. R.; Spencer, J. P. E.; Kuhnle, G.; Hahn, U.; Rice-Evans, C. A. Novel biomarkers of the metabolism of caffeic acid. Free Radical Biol. Med. 2001, 30, 1213-1222.
Rondinone, C. M.; Wang, L. M.; Lonnroth, P.; Wesslau, C.; Pierce, J. H.; Smith, U. Insulin receptor substrate (IRS) 1 is reduced and IRS-2 is the main docking protein for phosphatidylinositol 3-kinase in adipocytes from subjects with non-insulin-dependent diabetes mellitus. Proc. Natl. Acad. Sci. U S A. 1997, 94, 4171-4175.
Rosen, O. M. After insulin binds. Science 1987, 237, 1452-1457.
Saltiel, A. R.; Kahn C. R. Insulin signaling and the regulation of glucose and lipid metabolism. Nature 2001, 414, 799-806.
Scalbert, A.; Johnson, I. T.; Saltmarsh, M. Polyphenols: antioxidants and beyond. Am. J. Clin. Nutr. 2005, 81, 215S-217S.
Schmitz-Peiffer, C.; Craig, D. L.; Biden, T. J. 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. Cmem. 1999, 274, 24202-24210.
Senn, J. J.; Klover, P. J.; Nowak, I. A.; Mooney, R. A. Interleukin-6 induces cellular insulin resistance in hepatocytes. Diabetes 2002, 51, 3391-3399.
Shahid, G.; Hussain, T. GRK2 negatively regulates glycogen synthesis in mouse liver FL83B cells. J. Biol. Chem. 2007, 282, 20612-20620.
Shepherd, P. R.; Kahn, B. B. Glucose transporters and insulin action: implications for insulin resistance and diabetes mellitus. N. Engl. J. Med. 1999, 341, 248-257.
Shiba, T.; Higashi, N.; Nishimura, Y. Hyperglycaemia due to insulin resistance caused by interferon-gamma. Diabet. Med. 1998, 15, 435-436.
Solomon, S.; Buss, N.; Shull, J.; Monnier, S.; Majumdar, G.; Wu, J.; Gerling, I. Proteome of H-411E (liver) cells exposed to insulin and tumor necrosis factor-α: Analysis of proteins involved in insulin resistance. J. Lab. Clin. Med. 2005, 145, 275-283.
Sowwer, J. R.; Levy, J.; Zemel, M. B. Hypertension and diabetes. Med. Clin. N. Amer. 1988, 72, 1399-1414.
Stephens, J.; Pekala, P. Transcriptional repression of the C/EBP-alpha and GLUT4 genes in 3T3-L1 adipocytes by tumor necrosis factoralpha. Regulations is coordinate and independent of protein synthesis. J. Biol. Chem. 1992, 267, 13580-13584.
Stephens, J. M.; Lee, J.; Pilch, P. F. Tumor necrosis factor-alpha-induced insulin resistance in 3T3-L1 adipocytes is accompanied by a loss of insulin receptor substrate-1 and GLUT4 expression without a loss of insulin receptor-mediated signal transduction. J. Biol. Chem. 1997, 272, 971-976.
Steppan, C. M.; Bailey, S. T.; Bhat, S.; Brown, E. J.; Banerjee, R. R.; Wright, C. M.; Patel, H. R.; Ahima, R. S.; Lazar, M. A. The hormone resistin links obesity to diabetes. Nature 2001, 409, 307-312.
Summers, S. A.; Kao, A. W.; Kohn, A. D.; Backus, G. S.; Roth, R. A.; Pessin, J. E.; Birnbaum, M. J. The role of glycogen synthase kinase 3β in insulin-stimulated Glucose Metabolism. J. Biol. Chem. 1999, 274, 17934-17940.
Sutherland, C.; O’Brien, R. M.; Granner, D. K. New connections in the regulation of PEPCK gene expression by insulin. Phil. Trans. R. Soc. Lond. B. 1996, 351, 191-199.
Taylor, S. I.; Arioglu, E. Syndromes associated with insulin resistance and acanthosis nigricans. J.Basic Clin. Physiol. Pharmacol. 1998, 9, 419-439.
Tzeng, T. F.;. Liu, I. M.; Cheng J. T. Activation of opioid μ-receptors by loperamide to improve interleukin-6-induced inhibition of insulin signals in myoblast C2C12 cells. Diabetologia 2005, 48, 1386-1392.
Thorens, B.; Cheng, Z. Q.; Brown, D.; Lodish, H. F. Liver glucose transporter: a basolateral protein in hepatocytes and intestine and kidney cells. Am. J. Physiol. 1990, 259, C279-C285.
Tracey, K. J.; Cerami, A. Tumor necrosis factor, and other cytokines and disease. Annu. Rev. Cell Biol. 1993, 9, 317-343.
Tremblay, F.; Marette, A. Amino acid and insulin signaling via the mTOR/p70S6 kinase pathway. J. Biol. Chem. 2001, 276, 38052-38060.
Valentová, K.; Truong, N. T.; Moncion, A.; Waziers, I. D.; Ulrichová, J. Induction of glucokinase mRNA by dietary phenolic compounds in rat liver cells in vitro. J. Agric. Food Chem. 2007, 55, 7726-7731.
Vandenabeele, P.; Declercq, W.; Beyaert, R.; Fiers, W. Two tumor necrosis factor receptors: structure and function. Trends Cell. Biol. 1995, 5, 392-399.
Villar-Palasi, C.; Guinovart, J. J. The role of glucose 6-phosphate in the control of glycogen synthase. FASEB J. 1997, 11, 544-558.
White, M. F.; Kahn, C. R. The insulin signaling system. J. Biol. Chem. 1994, 269, 1-4.
White, M. F. Insulin signaling in health and disease. Science 2003, 302, 1710-1711.
Wild, S.; Roglic, G.; Green, A.; Sicree, R.; King, H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004, 27, 1047-1053.
Wilkins, M. R.; Sanchez, J. C.; Gooley, A. A.; Appel, R. D.; Humphery-Smith, I.; Hochstrasser, D. F.; Williams, K. L. Progress with proteome projects: why all proteins expressed by a genome should be identified and how to do it. Biotechnol. Genet. Eng. Rev. 1995, 13, 19-50.
Winder, W. W.; Hardie, D. G. AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am. J. Physiol. 1999, 277, E1-E10.
Yoon, J. C.; Puigserver, P.; Chen, G.; Donovan, J.; Wu, Z.; Rhee, J.; Adelmant, G.; Stafford, J.; Kahn, C. R.; Granner, D. K.; Newgard, C. B.; Spiegelman, B. M. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 2001, 413, 131-138.
Yoshinaga, T. A. Morphological study on the mechanism of insulin-release, using sulfonylurea, l-leucine, and alpha-ketocarboxylic acids. Nippon Naibunpi Gakkai Zasshi - Folia Endocrinol. Jap. 1968, 44, 741-749.
Zick, Y. Insulin resistance: a phosphorylation-based uncoupling of insulin signaling. Trends Cell Biol. 2001, 11, 437-441.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top