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研究生:吳青蓉
研究生(外文):Wu, Ching-Jung
論文名稱:黃金銀耳酸性多醣對FL83B小鼠肝臟細胞具胰島素增敏功效
論文名稱(外文):Enhancing Insulin Sensitivity in FL83B Hepatocytes by Glucuronoxylomannan purified from Tremella mesenterica
指導教授:盧錫祺盧錫祺引用關係
指導教授(外文):Lu, Hsi-Chi
口試委員:陳春榮蔡政志顧野松謝長奇
口試委員(外文):Chen, Chun-JungTsai, Cheng-ChihGu, Ye-SongHsieh, Chang-Chi
口試日期:2011-05-27
學位類別:碩士
校院名稱:東海大學
系所名稱:食品科學系
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:2011
畢業學年度:99
語文別:中文
論文頁數:99
中文關鍵詞:第二型糖尿病黃金銀耳酸性多醣胰島素阻抗葡萄糖攝入胰島素傳訊肝醣合成
外文關鍵詞:Type 2 diabetes mellitusTremella mesentericaglucuronoxylomannaninsulin resistanceglucose uptakeinsulin signalglycogen content
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第二型糖尿病為胰島素作用缺失導致醣類、脂肪及蛋白質代謝異常之慢性疾病,佔所有相關病例九成以上。為數更多的未病群面臨逐漸惡化而仍可逆之血糖過高及胰島素阻抗,如能協助增進敏感性可避免演進至疾病狀態。肝臟可調控葡萄糖之合成及分解而為血糖恆定重要臟器,而蕈菇類多醣體則在過去研究中證實可能透過胰島素增敏而改善實驗動物之高血糖狀況。黃金銀耳富含多醣體達60%以上,其中純化後之酸性多醣GXM即佔子實體20%以上,並已於大鼠模式顯示對於正常及糖尿病狀態具有顯著增敏功效。為進一步以作用濃度及時間等各項參數探討酸性多醣體於正常及阻抗態細胞降血糖之機制,本研究以高糖誘導FL83B小鼠肝細胞產生胰島素阻抗,分別在葡萄糖攝入、肝醣合成及胰島素傳訊等層面進行觀察。流式細胞分析及西方轉漬顯示,高葡萄糖培養顯著降低FL83B細胞帶入葡萄糖擬似物2-NBDG以及Akt 磷酸化。黃金銀耳GXM之添加可明顯提高正常及阻抗細胞2-NBDG之帶入。西方轉漬及同步定量PCR分析亦證實GXM可顯著提昇第二型葡萄糖轉運蛋白及葡萄糖激酶之蛋白質及mRNA表現。肝醣含量分析顯示GXM能隨作用時間增加而促進正常細胞及阻抗細胞肝醣合成。GXM對於胰島素傳訊亦能顯著提昇,包括正常及阻抗細胞Akt磷酸化,胰島素受體、PI3K、Akt 蛋白質表現量、胰島素受體mRNA表現量等。若經胰島素共同刺激,則上述基因表現量大多具加乘效果。本研究證實,黃金銀耳多醣體可能透過影響肝細胞葡萄糖轉運、葡萄糖代謝利用、胰島素傳訊等,協同減輕胰島素阻抗,藉而增加帶入葡萄糖之能力。
Type 2 diabetes mellitus is a chronic disease associated with abnormality in carbohydrate, protein and lipid metabolism and is caused by ineffectiveness in insulin action. About 90% of the diabetic incidence belongs to type 2 diabetes. Even more are suffering from deteriorating yet reversible prediabetes hyperglycemia and insulin resistance, which could be averted by insulin-sensitizing remedies. Liver plays pivotal roles in glucose homeostasis by regulating glucose metabolism and mobilization; whereas mushroom’s glycan has been shown to possess antidiabetic activity, possible through enhancing insulin sensitivity, in experimental animal models. Tremella mesenterica is made of more than 60% glycan and containing 20% of glucuronoxylomannan (GXM) when purified from fruiting bodies, and has been found to improve insulin signaling in normal and diabetic rats. To further investigate the antiglycemic mechanisms of GXM under series of incubation concentrations and time, glucose uptake, glycogen content, insulin signaling were observed in mouse hepatocyte FL83B with or without the induction of insulin resistance by incubation with high glucose. As showed in flow cytometry and Western blotting, treating FL83B cells with high glucose significantly reduced the uptake of glucose analogue 2-NBDG, and the phosphorylation of Akt protein. GXM from T. mesenterica significantly enhance NBDG uptake by cells in normal or insulin resistant status. Results from Western blotting and real-time PCR also suggested the protein and mRNA expressions of glucose transporter-2 and glucokinase were greatly upregulated in FL83B cells after addition of GXM. Glycogen synthesis both in normal and in insulin resistant cells was likely increased in parallel with the prolonged incubation with GXM, as revealed by analysis of glycogen content. GXM showed similar and profound effects on upregulating insulin signaling in normal and insulin-resistant cells when examining the phosphorylation status of Akt, protein expression level of insulin receptor, PI3K, Akt and mRNA expression level of insulin receptor. Most of the gene expressions were further enhanced in the presence of insulin. Data obtained in this study suggested that the GXM of T. mesenterica may enhance the insulin sensitivity in hepatocytes as manifested by elevated glucose uptake, and acted possibly through improved glucose transportation, glucose utilization/metabolism, and insulin signaling.
摘要...........................................................................................................................1
英文摘要...................................................................................................................2
一、前言..................................................................................................................4
1-1 糖尿病................................................................................................................4
1-1-1 糖尿病的分類.................................................................................................4
1-1-2 糖尿病診斷.....................................................................................................6
1-1-3 糖尿病的治療.................................................................................................6
1-2 胰島素與血糖恆定之維持..................................................................................7
1-2-1 葡萄糖之生理恆定作用.................................................................................7
1-2-2 胰島素的結構.................................................................................................8
1-2-3 胰島素的分泌.................................................................................................8
1-2-4 胰島素的作用.................................................................................................8
1-2-5 胰島素抗性.....................................................................................................9
1-2-6 胰島素訊息傳遞路徑及其分子機制...........................................................10
1-3 胰島素與醣類代謝之影響.................................................................................15
1-3-1 肝臟中葡萄糖代謝途徑...............................................................................15
1-3-2 肝醣合成之調節...........................................................................................17
1-3-3 糖質新生與葡萄糖分解之調節...................................................................17
1-4 高糖誘發第二型糖尿病模式之機制.................................................................19
1-4-1 以細胞模式探討胰島素阻抗之研究...........................................................19
1-4-2 高糖誘發之胰島素阻抗...............................................................................19
1-5 黃金銀耳與其生理功效.....................................................................................21
1-5-1 黃金銀耳介紹...............................................................................................21
1-5-2 酸性多醣生理功效之研究...........................................................................21
1-6 研究動機與實驗架構........................................................................................23
二、材料方法 25
2-1 實驗材料............................................................................................................25
2-1-1 小鼠細胞株...................................................................................................25
2-1-2 細胞培養基...................................................................................................25
2-1-3 人類胰島素溶液...........................................................................................25
2-1-4 葡萄糖擬似物...............................................................................................25
2-1-5 黃金銀耳Tremella mesenterica酸性多醣....................................................26
2-1-6細胞培養其他藥品........................................................................................26
2-1-7 蛋白質分析試劑...........................................................................................26
2-1-8 主要儀器及設備.........................................................................................28
2-2 實驗方法...............................................................................................................28
2-2-1 黃金銀耳酸性多醣分子量測定...................................................................28
2-2-1 細胞培養與繼代...........................................................................................29
2-2-2 誘導FL83B細胞產生胰島素抗性................................................................29
2-2-3 細胞毒性試驗...............................................................................................30
2-2-4 FL83B細胞葡萄糖帶入量分析....................................................................30
2-2-5萃取FL83B細胞之胞內肝醣.......................................................................32
2-2-6 抽取FL83B細胞RNA...................................................................................32
2-2-7 cDNA製備......................................................................................................32
2-2-8 同步定量聚合酶連鎖反應...........................................................................33
2-2-9 FL83B細胞之蛋白質萃取.............................................................................34
2-2-10 蛋白質定量.................................................................................................34
2-2-11 西方轉漬法.................................................................................................34
2-3 統計分析.............................................................................................................35


三、結果
3-1不同濃度之GXM對肝臟細胞FL83B毒性測定.................................................38
3-2黃金銀耳酸性多醣分子量測定............................................................................38
3-3葡萄糖擬似物2-NBDG攝入量............................................................................40
3-3-1不同濃度葡萄糖誘導FL83B產生胰島素阻抗............................................40
3-3-2 酸性多醣對FL83B細胞攝入2-NBDG影響...............................................41
3-3-3 酸性多醣對胰島素阻抗FL83B細胞之2-NBDG攝入量影響…………..42
3-4胰島素傳訊............................................................................................................44
3-4-1 高糖誘導FL83B胰島素阻抗對於Akt及phospho-Akt(Ser473)蛋白質相對
表現量之影響................................................................................................44
3-4-2 酸性多醣對於正常及阻抗狀態FL83B細胞之胰島素受體(IR)、磷酸肌醇
激酶PI3-kinase及PKB/Akt蛋白質表現影響..............................................45
3-4-3 400ppm酸性多醣不同作用時間下,FL83B細胞之胰島素受體(IR) mRNA
相對表現量....................................................................................................54
3-4-4 400ppm酸性多醣不同作用時間下,胰島素受體(IR)蛋白質相對表現量..56
3-5葡萄糖轉運及代謝................................................................................................59
3-5-1 酸性多醣對於正常及阻抗狀態FL83B細胞葡萄糖轉運蛋白(GLUT2)及葡
萄糖激酶(GK)蛋白質相對表現量...............................................................59
3-5-2 400ppm酸性多醣不同作用時間下,FL83B細胞葡萄糖轉運蛋白(GLUT2)
及葡萄糖激酶(GK)之mRNA相對表現量...................................................63
3-5-3 400ppm酸性多醣不同作用時間下,FL83B細胞葡萄糖轉運蛋白(GLUT2)
及葡萄糖激酶(GK)之蛋白質相對表現量...................................................67
3-6肝醣合成量分析....................................................................................................71
3-6-1 添加不同濃度酸性多醣其肝醣合成量分析...............................................71
3-6-2 添加不同濃度酸性多醣於高糖阻抗其肝醣合成量分析...........................71
3-6-3 400ppm酸性多醣不同作用時間,正常及阻抗態其肝醣合成分析.............72
四、討論........................................................................................................................74
4-1 酸性多醣分子量...................................................................................................74
4-2 胰島素傳訊...........................................................................................................74
4-3 葡萄糖轉運及代謝及葡萄糖擬似物2-NBDG攝入量分析................................77
4-4 肝醣合成量...........................................................................................................79
4-5 代謝率換算...........................................................................................................79
4-6 總論.......................................................................................................................80
五、未來展望................................................................................................................84
附圖一 多醣分子量之標準曲線。..............................................................................85
附圖二 促發炎細胞激素在肥胖相關胰島素阻抗發展過程可能參與之機制。......86
附圖三 動物實驗設計流程。......................................................................................87
附圖四 動物實驗肝臟檢體各蛋白質表現結果........................................................88
參考文獻......................................................................................................................90

1.呂淑芳、宮昭雲、傅偉光。2001。靈芝中之水溶性粗多醣分析方法之研究。台灣農業化學與食品科學39:153-161。
2.杜巍、李元瑞、袁靜。食藥用菌多醣生物活性結構的關係。2002。中國食用菌 21:28-30。
3.林俊仁。肥胖關聯之炎症與胰島素抗性。2004。食品工業發展研究所專題報告。第36卷第6期42-54新竹 台灣。
4.胡智柏。口服降血糖製劑與天然調控血糖物質。2002。食品工業發展研究所專題報告。第34卷第6期19-37新竹 台灣。
5.國立自然科學博物館,自然與人文數位博物館。http://digimuse.nmns.edu.tw/
6.陳國群。糖尿病治療藥物。1999。藝軒圖書出版社。第1-5頁。
7.黃仁彰。食藥用菇類保健食品之研發。食藥用菇類的培養與應用。1998。食品工業發展研究所專題報告 新竹 台灣。
8.劉波。中國藥用真菌。1978。第1版。
9.鄭汝翔。黃金銀耳於糖尿病大鼠模式肝臟中降血糖機制之探討。2010。東海大學食品科學研究所,碩士論文。
10.賴惠蘭。黃金銀耳於糖尿病大鼠模式肌肉中降血糖機制之探討。2010。東海大學食品科學研究所,碩士論文。
11.顏巧雯。篩選及研究與B型肝炎表面抗原交互作用之蛋白。2003。國立成功大學生物化學研究所,碩士論文。
12. Ahn YH, Yoon DJ, Han GS, Lee BG. 1993. Cloning and expression of rat liver type glucose transporter and translocation by insulin in Chinese hamster ovary cells. Yonsei Med J. 34: 117-125
13.Bouche C, Serdy S, Kahn CR, Goldfine AB. 2004. The cellular fate of glucose and its relevance in type 2 diabetes. Endocr Rev. 25:807-30.
14.Brownlee M. 2005. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54: 1615-1625.
15.Butler AA, LeRoith D. 2001. Tissue-specific versus generalized gene targeting of the igf1 and igf1r genes and their roles in insulin-like growth factor physiology. Endocrinology. 142: 1685-1688
16.Byrne CD, 2000. Does tumour necrosis factor-α influence insulin sensitivity in skeletal muscle. Clin. Sci. 99: 329-330.
17.Ceriello A. 2003. New insights on oxidative stress and diabetic complications may lead to a “causal” antioxidant therapy. Diabetes Care. 26:1589-1596.
18.Cheg HL, Huang HK, Chang CI, Tsai CP, Chou CH,. 2008. 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. 56: 6835–6843
19.Chen YW, Lo HC, Yang JG, Chien CH, Lee SH, Tseng CY, Huang BM. 2006. The regulatory mechanism of Tremella mesenterica on steroidogenesis in MA-10 mouse Leydig tumor cells. Life Sci. 79: 584-90.
20.Cheng AY, Fantus IG. 2005.Oral antihyperglycemic therapy for type 2 diabetes mellitus. CMAJ. 172: 213-226.
21.Cho H, Mu J, Kim JK, Thorvaldsen JL, Chu Q, Crenshaw EB, Kaestner KH, Bartolomei MS, Shulman GI, Birnbaum MJ. 2001. Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKBβ). Science. 292: 1728-1731
22.Cichy SB, Uddin S, Danilkovich A,Guo S, Klippel A, Unterman TG. 1998.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. 273: 6482-6487.
23. Collier JJ, Scott DK. 2004. Sweet changes: glucose homeostasis can be altered by manipulating gene controlling hepatic glucose metabolism. J. Mol. Endocrinol. 18: 1051-1063
24.Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA. 1995. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 378: 785-789.
25.DeFronzo RA. 1988. The triumvirate: beta-cell, muscle, liver: a collusion responsible for NIDDM. Diabetes. 37: 667-687.
26.Dietze D, Koenen M, Rohrig K, Horikoshi H, Hauner H, Eckel J. 2002. Impairment of insulin signaling in human skeletal muscle cells by co-culture with human adipocytes. Diabetes. 51: 2369-2376.
27.Downward J. 1998.Mechanisms and consequences of activation of protein kinase B/Akt. Curr Opin Cell Biol. 10: 262-267.
28.Eisenberg ML, Maker AV, Slezak LA, Nathan JD, Scritharan KC, Jena BP, Geibel JP, Andersen DK. 2005. Insulin receptor (IR) and glucose transporter 2 (GLUT2) proteins forms a complex on the rat hepatocyte membrane. Cell Physiol Biochem. 15: 51-58.
29.Ferrer JC, Favre C, Gomis RR, Fernandez-Novell JM, Garica-Rocha M, Dela Iglesia N, Cid E, Guinovart JJ. 2003. Control of glycogen deposition. FEBS Lett. 546: 127-132
30.Fink RI, Wallace P, Brechtel G, Olefsky JM. 1992. Evidence that glucose transport is rate-limiting for in vivo glucose uptake. Metabolism. 41: 897–902.
31.Fisher SJ, Kahn C. 2003. Insulin signaling is required for insulin’s direct and indirect action on hepatic glucose production. J Clin Invest. 111: 463-468
32.Gerich JE. 1998. The genetic basis of type 2 diabetes mellitus: impaired insulin secretion versus impaired insulin sensitivity. Endocr. Rev. 19: 491-503.
33.Hah J, Jo I, Chakrabarti R, Jung CY. 1992. Demonstration of an insulin –insensitive storage pool of glucose transporters in rat hepatocytes and HepG2 cells. J Cell Physiol. 152: 56-63
34.Hotamisligil GS, Murray DL, Choy LN, Spiegelman BM. 1994.Tumor necrosis factor alpha inhibits signaling from the insulin receptor. Proc. Natl. Acad. Sci. 91: 4854-4858
35.Huang DW, Shen SC, Wu JSB, 2009. Effects of caffeic acid and cinnamic acid on glucose uptake in insulin-resistant mouse hepatocytes. J. Agric. Food Chem. 57: 7687–7692
36.Jiang ZY, Zhou QL, Coleman KA, Chouinard M, Boese Q, Czech MP ,2003, Insulin signaling through Akt protein kinase B analyzed by small interfering RNA-mediated gene silencing. Proc. Natl. Acad. Sci. 100: 7569-7574.
37.Khondkar P, Aidoo KE, Tester RF. 2002. Sugar profile of extracellular polysaccharides from different Tremella species. Int J Food Microbiol. 79: 121-129.
38.Kiho T, Hui J, Yamane A, Ukai S. 1993. Polysaccharides in fungi. XXXII. Hypoglycemic activity and chemical properties of a polysaccharide from the cultural mycelium of Cordyceps sinensis. Biol Pharm Bull. 16: 1291-1293.
39.Kiho T, Morimoto H, Kobayashi T, Usui S, Ukai S, Aizawa K, Inakuma T. 2000. Effect of a polysaccharide (TAP) from the fruiting bodies of Tremella aurantia on glucose metabolism in mouse liver. Biosci. Biotechnol. Biochem. 64: 417-419.
40.Kiho T, Morimoto H, Sakushima M, Usui S, Ukai S. 1995. Polysaccharides in fungi. XXXV. Anti diabetic activity of an acidic polysaccharide from the fruiting bodies of Tremella aurantia. Biol Pharm Bull. 18: 1627-1629.
41.Kiho T, Ookubo K, Usui S, Ukai S, Hirano K. 1999. Structural features and hypoglycemic activity of a polysaccharide (CS-F10) from the cultured mycelium of Cordyceps sinensis. Biol Pharm Bull. 22: 966-970.
42.Kiho T, Tsujimura Y, Sakushima M, Usui S. Ukai S. 1994. Polysaccharides in fungi. XXXIII. Hypoglycemic activity of an acidic polysaccharide (AC) from Tremella fuciformis. Yakugaku Zasshi. 114: 308-315.
43.Kumar N, Dey CS, 2003, Development of insulin resistance and reversal by thiazolidinediones in C2C12 skeletal muscle cells. Biochem. Pharmacol. 65: 249-257.
44.Lawrence JC, Roach PJ. 1997. New insights into the role and mechanism of glycogen synthase activation by insulin. Diabetes. 46: 541-7.
45.Lawrence, 1961.Microdetermination of glycogen with anthrone reagent. Department of Anatomy, University of Kansas, Received for publication April 21
46.Leclercq IA, Morais ADS, Schroyen B, Hul NV, Geerts A. 2007. Insulin resistance in hepatocytes and sinusoidal liver cell : mechanisms and consequences. J. Hepatol. 47: 142-156.
47.Li SP, Zhang GH, Zeng Q, Huang ZG, Wang YT, Dong TTX, Tsim KWK. 2006. Hypoglycemic activity of polysaccharide, with antioxidation, isolated from cultured Cordyceps mycelia. Phytomedicine. 13: 428–433
48.Lietzke SE, Bose S, Cronin T, Klarlund J, Chawla A, Czech MP, Lambright DG. 2000. Structural basis of 3-phosphoinositide recognition by pleckstrin homology domains. Mol. Cell. 6: 385-394.
49.Lillioja S, Mott DM, Howard BV, Bennett PH, Yki-Jarvinen H, Freymond D, Nyomba BL, Zurlo F, Swinburn B, Bogardus C. 1988. Impaired glucose tolerance as a disorder of insulin action. Longitudinal and cross-sectional studies in Pima Indians. N. Engl. J. Med. 318: 1217-1225.
50.Lin CL, Lin JK. 2008. Epigallocatechin gallate (EGCG) attenuates high glucose-induced insulin signaling blockade in human hepG2 hepatoma cells. Mol. Nutr. Food Res. 52: 930 – 939
51.Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25: 402-408.
52.Lo HC, Chen YW, Chien CH, Tseng CY, Kuo YM, Huang BM. 2005. Effects of Tremella mesenterica on steroidogenesis in MA-10 mouse Leydig tumor cells. Arch Androl. 51: 285-94.
53.Lo HC, Tsai FA, Wasser SP, Yang JG, Huang BM. 2006. Effects of ingested fruiting bodies, submerged culture biomass, and acidic polysaccharide glucuronoxylomannan of Tremella mesenterica Retz.:Fr. on glycemic responses in normal and diabetic rats. Life Sci. 78: 1957-1966.
54.Ma L, Lin ZB, 1992. Effect of Tremella polysaccharide on IL-2 production by mouse splenocytes. Yao Xue Xue Bao. 27: 1-4.
55.Mao XL,1998. Economic Fungi of China. Academic Press, Beijing, pp. 458.
56.Miyake K, Ogawa W, Matsumoto M, Takehiro N, Sakaue H, Kasuga M. 2002. Hyperinsulinemia, glucose intolerance, and dyslipidemia induced by acute inhibition of phosphoinositide 3-kinase signaling in the liver. J. Clin. Invest. 110: 1483-1491
57.Miyake K, Ogawa W, Matsumoto M, Takehiro N, Sakaue H, Kasuga M. 2002. Hyperinsulinemia, glucose intolerance, and dyslipidemia induced by acute inhibition of phosphoinositide 3-kinase signaling in the liver. J. Clin. Invest. 110: 1483-1491
58.Mueckler M. 1994. Facilitative glucose transporters. Eur. J. Biochem. 219: 713-725.
59.Nordlie RC, Fostem JD, Lange AJ. 1999. Rrgulation of glucose production by the liver. Annu. Rev. Nutr. 19: 379-406
60.Patiag D, Gray S, Idris I, Donnelly R, 2000, Effect of tumour necrosisfactor-α and inhibition of protein kinase C on glucose uptake in L6 myoblasts. Clin. Sci. 99: 303-307.
61.Pilkis SJ, Granner DK. 1992. Molecular physiology of the regulation of hepatic gluconeogenesis and glycolysis. Annu. Rev. Physiol. 54: 885-909.
62.Reagan-Shaw S., Nihal M., Ahmad N. 2007. Dose translation from animal to human studies revisited. FASEB J. 22: 659–661
63.Reshetnikov SV, Wasser SP, Nevo E, Duckman I, Tsukor K. 2000. Medicinal value of the genus Tremella Pers. (Heterobasidiomycetes). Int J Med Mushr. 2: 169-193.
64.Rojas FA, Hirata AE, Saad MJA. 2001. Regulation of IRS-2 tyrosine phosphorylation in fasting and diabetes. Mol. Cell. Endocrinol. 183: 63-69
65.Rui L, Aguirre V, Kim J.K, Shulman GI, Lee A, Corbould A, Dunaif A, White MF. 2001. Insulin/IGF-1 and TNF-alpha stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways. J.Clin. Invest. 107: 181-189.
66.Rutter GA. 2000. Diabetes: The importance of the liver. Curr. Biol. 10: 736-738
67.Saltiel AR, Khan CR. 2001. Insulin signaling and the regulation of glucose and lipid metabolism. Nature. 414: 799-806.
68.Saltiel AR, Pessin JE. 2002. Insulin signaling pathways in time and space. Trends Cell Biol. 12: 65-71.
69.Schinner S, Scherbaum WA, Bornstein SR, Barthel A. 2005. Molecular mechanisms of insulin resistance. Diabet Med. 22: 674-682.
70.Sesti G, Federici M, Hribal ML, Lauro D, Sbraccia P, Lauro R. 2001. Defects of the insulin receptor substrate (IRS) system in human metabolic disorders. FASEB J. 15: 2099-2111
71.Shimokawa T, Kagami M, Kato M, Kurosaki E, Shibasaki M, Katoh M ,2000, Effect of YM-126414 on glucose uptake and redistribution of glucose transporter isotype 4 in muscle cells. Eur. J. Pharmacol. 410: 1-5.
72.Shulman GI. 2000. Cellular mechanisms of insulin resistance. J. Clin. Invest. 106: 171-176.
73.Taniguchi CM, Ueki K, Kahn R. 2005. Complementary roles of IRS-1 and IRS-2 in the hepatic regulation of metabolism. J Clin Invest. 115: 718-727.
74.Valverde AM, Navarro P, Teruel T, Conejo R, Benito M, Lorenzo M. 1999. Insulin and insulin-like growth factor I up-regulate GLUT4 gene expression in fetal brown adipocytes, in a phosphoinositide 3-kinase-dependent manner. Biochem. J. 337: 397-405.
75.Vinogradov E, Petersen BO, Duus JO, Wasser S, 2004. The structure of the glucuronoxylomannan produced by culinary-medicinal yellow brain mushroom (Tremella mesenterica Ritz.:Fr., Heterobasidiomycetes) grown as one cell biomass in submerged culture. Carbohydr Res. 339: 1483-1489.
76.Wang Z, Lv J, Zhang R, Zhu Y, Zhu D, Sun Y, Zhu J, Han X. 2006. Co-culture with fat cells induces cellular insulin resistance in primary hepatocytes. Biochem Biophys Res Commun. 345: 976-983.
77.Warram JH, Martin BC, Krolewski AS, Soeldner JS, Kahn CR. 1990. Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic patients. Ann. Intern. Med. 113: 909-915.
78.White MF, Kahn CR. 1994. The insulin signaling system. J. Biol. Chem. 269: 1-4.
79.White MF. 2002. IRS proteins and the common path to diabetes. Am J Physiol Endocrinol Metab. 283: 413-422
80.Yan SD, Schmidt AM, Anderson GM, Zhang J, Bertt J, Zou YS, Pinsky D. Stern D. 1994. Enhanced cellular oxidant stress by the interaction of advanced glycation endproducts with their receptors/binding proteins. J. Biol. Chem. 269: 9889-9897
81.Yang ZZ, Tschopp O, Baudry A, Dümmler B, Hynx D, Hemmings BA. 2004. Physiological functions of protein kinase B/Akt. Biochem. Soc. Trans. 32: 350-354
82.Yki-Jarvinen H, Vuorinen-Markkola H, Koranyi L, Bourey R, Tordjman K, Mueckler M, Permutt AM, Koivisto VA. 1992. Defect in insulin action on expression of the muscle/adipose tissue glucose transporter gene in skeletal muscle of type 1 diabetic patients. J. Clin. Endocrinol. Metab. 75: 795–799.
83.Yoshioka K, Oh KB, Saito M, Nemoto Y, Matsuoka H. 1996. Evaluation of 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-Dglucose, a new fluorescent derivative of glucose, for viability assessment of yeast Candida albicans. Appl. Microbiol. Biotechnol. 46: 400– 404.
84.Yoshioka K, Saito M, Oh KB, Nemoto Y, Matsuoka H, Natsume M. 1996. Intracellular fate of 2-NBDG, a fluorescent probe for glucose uptake activity, in Escherichia coli cells. Biosci. Biotechnol. Biochem. 60: 1899– 1901.
85.Yoshioka K, Takahashi T, Homma T, Saito M, Oh KB, Nemoto Y. 1996. A novel fluorescent derivative of glucose applicable to the assessment of glucose uptake activity of Escherichia coli. Biochim. Biophys. Acta. 1289: 5– 9.
86.Yu ZW, Buren J, Enerback S, Nilsson E, Riksson JW ,2001, Insulin can enhance GLUT4 gene expression in 3T3-F442A cells and this effect is mimicked by vanadate but counteracted by cAMP and high glucose-potential implications for insulin resistance. Biochim. Biophys. Acta. 1535: 174-185.
87.Yuen VG, McNeill JH . 2000, Comparison of the glucose oxidase method for glucose determination by manual assay and automated analyzer. J. Pharmacol. Toxicol. Methods. 44: 543-546.
88.Zdychova J, Komers R. 2005. Emerging role of akt kinase/protein kinase B signaling in pathophysiology of diabetes and its complications. Physiol. Res. 54: 1-16.
89.Zick Y. 2001. Insulin resistance: a phosphorylation-based uncoupling of insulin signaling. Trends Cell Biol. 11: 437-441.
90.Zierath JR, Kawano Y . 2003. The effect of hyperglycaemia on glucose disposal and insulin signal transduction in skeletal muscle. Best. Pract. Res. Clin. Endocrinol. Metab. 17: 385-398.
91.Zimmet PZ. 1999. Diabetes epidemiology as a trigger to diabetes research. Diabetologia. 42: 499-518.
92.Zou CH, Wang YJ, Shen ZF. 2005. 2-NBDG as a fluorescent indicator for direct glucose uptake measurement. J. Biochem. Biophys. Methods. 64: 207–215


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