(18.206.177.17) 您好!臺灣時間:2021/04/23 05:50
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:許雅嵐
研究生(外文):Ya-Lan Hsu
論文名稱:短鏈脂肪酸對棕櫚酸誘發之C2C12肌肉細胞發炎反應及胰島素阻抗之影響
論文名稱(外文):The effects of short chain fatty acids on palmitate-induced inflammation and insulin resistance in C2C12 skeletal muscle cells
指導教授:劉凱莉劉凱莉引用關係
指導教授(外文):Kai-Li Liu
學位類別:碩士
校院名稱:中山醫學大學
系所名稱:營養學研究所
學門:醫藥衛生學門
學類:營養學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:中文
論文頁數:83
相關次數:
  • 被引用被引用:0
  • 點閱點閱:271
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
長期西式飲食型態及靜態生活方式,使體重增加,影響胰島素的敏感性,研究資料證實,胰島素阻抗是罹患代謝性症候群及糖尿病的危險因子,雖然肥胖造成胰島素阻抗機轉不是很清楚,但與血漿過多的游離脂肪酸及發炎反應有密切的關係。短鏈脂肪酸 —丙酸、丁酸,為人體腸道細菌發酵代謝纖維質的產物,可以調節腸道免疫功能、降低膽固醇及抗發炎反應。本研究目的,主要探討短鏈脂肪酸對飽和棕櫚酸誘發C2C12肌肉細胞發炎反應及胰島素阻抗之影響。實驗結果顯示,給予C2C12肌肉細胞丙酸及丁酸,可以降低棕櫚酸誘發的磷酸化protein kinase c-θ、extracellular-regulated protein kinase 1/2及P38 mitogen-activated kinase,減少轉錄因子nuclear factor-κB活性,降低促發炎反應物質cyclooxygenase-2、interleukin-6、tumor necrosis factor-α表現。在基礎狀態下,丙酸及丁酸可恢復棕櫚酸降低磷酸化AMP-activated protein kinase 及Akt substrate of 160 kDa。此外,肌肉細胞給予棕櫚酸,明顯降低胰島素誘發的磷酸化Akt及減少肌肉細胞對葡萄糖的攝取,造成胰島素阻抗,處理丙酸及丁酸,可以恢復棕櫚酸抑制磷酸化Akt,增加肌肉細胞對葡萄糖的攝取。經由本研究證實,短鏈脂肪酸在C2C12肌肉細胞,具有抑制棕櫚酸誘發的發炎反應及改善胰島素阻抗之功效。

The western style dietary pattern and inactive lifestyle have been shown to increase insulin resistance and to be a risk factor for developing metabolic syndrome and diabetes. It was reported that elevated plasma free fatty acid is response to the inflammation and insulin resistance in diabetic patients and nondiabetic subjects. Propionate (PrA) and butyrate (BuA) short chain fatty acids (SCFAs) are metabolic products of fiber by intestinal bacteria fermentation, SCFAs could regulate immune function and inflammation. Here, the effects of SCFAs on palmitate (PA) -induced inflammation and insulin resistance in C2C12 skeletal muscle cells were examined. Exposure of C2C12 cells to PA enhanced phosphylation of protein kinase c-θ, mitogen-activated protein kinase. Moreover, PA increased activity of transcription factor nuclear factor-κB and production of proinflammatory mediators, such as, cyclooxygenase-2, interleukin-6 and tumor necrosis factor-α. PrA and BuA reversed palmitate down-regulated of phosphorylation of AMP-activated protein kinase and Akt substrate of 160 kDa in basal state. PA-induced insulin resistance as the evidence by decrease phosphylation of Akt activation and glucose uptake in insulin stimulated C2C12 cells. Co-incubation of C2C12 cells with PA, PrA and BuA reversed PA induced inflammatory events and insulin resistance. These data demonstrated that SCFAs are effective in inhibition of PA-induced inflammation and insulin resistance in C2C12 skeletal muscle cells.

目錄---------------------------------------------------------I
圖次--------------------------------------------------------IV
縮寫表-----------------------------------------------------VI
中文摘要--------------------------------------------------IX
英文摘要-------------------------------------------------- XI
前言---------------------------------------------------------1
一、發炎反應----------------------------------------------1
二、發炎反應及相關調控路徑--------------------------1
(1)Protein Kinase C (PKC)---------------------1
(2)Mitogen-Activated Protein Kinase (MAPKs)-----3
(3)Nuclear Factor kappa B (NF-κB)----------4
(4)促發炎物質------------------------------------------5
(a)Interleukin-6(IL-6)和 Tumor Necrosis Factor-α(TNF-α)--------------------------------------------------------------5
(b)Cyclooxygenase(COX)---------------------6
三、脂肪酸簡介------------------------------------------7
四、脂肪酸與發炎反應及胰島素阻抗----------------8
(1)飽和脂肪酸與發炎反應及胰島素阻抗---------8
(2)短鏈脂肪酸與發炎反應及胰島素阻抗---------9
五、胰島素阻抗-----------------------------------------11
六、發炎反應及胰島素阻抗------------------------12
七、胰島素阻抗及相關調控路徑---------------------13
(1)Adenosine monophosphate-activated protein kinase(AMPK)--------------------------------------------------------------13
(2)Akt substrate of 160 kDa (AS160)-------14
(3)Akt--------------------------------------------------14
(4)Glucose transporter (GLUT)--------------15
實驗目的--------------------------------------------------17
實驗架構--------------------------------------------------18
實驗材料--------------------------------------------------19
實驗方法--------------------------------------------------28
一、細胞培養---------------------------------------------28
二、細胞存活率分析------------------------------------29
三 、細胞蛋白質表現量分析---------------------------30
四、Reverse Transcription-Polymerase Chain Reaction (Real- time PCR)-----------------------------------------------------------33
五、Electrophoretic Mobility Shift Assay (EMSA)---35
六、 Plasmid Purification (質體DNA之純化 )---37
七、Transiet Transfection / SEAP assay-------38
八、Glucose Uptake---------------------------------40
統計分析------------------------------------------------41
實驗結果------------------------------------------------42
討論------------------------------------------------------53
結論------------------------------------------------------58
結果圖表------------------------------------------------59
參考文獻------------------------------------------------74
附件------------------------------------------------------83


1. 曾岐元,最新病理學,匯華圖書出版股份有限公司,2005。
2. Cosentino-Gomes D, Rocco-Machado N, Meyer-Fernandes JR:
Cell Signaling through Protein Kinase C Oxidation and Activation. International Journal of Molecular Sciences 2012, 13:10697-10721.
3. Nakamura S-i: Phosphatidylcholine hydrolysis and protein kinase C activation for intracellular signaling network. Journal of Lipid Mediators Cell Signalling 1996, 14:197-202.
4. Jove M, Planavila A, Sanchez RM, Merlos M, Laguna JC, Vazquez-Carrera M: Palmitate induces tumor necrosis factor-alpha expression in C2C12 skeletal muscle cells by a mechanism involving protein kinase C and nuclear factor-kappaB activation. Endocrinology 2006, 147:552-561.
5. Jove M, Planavila A, Laguna JC, Vazquez-Carrera M: 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 2005, 146:3087-3095.
6. Kolapo M Ajuwon MES: Palmitate Activates the NF-[kappa]B Transcription Factor and Induces IL-6 and TNF-alpha Expression in 3T3-L1 Adipocytes. the Journal of Nutrition 2005, 8:1841-1846.
7. Margaret E. Griffin MJM, Gary W. Cline, Kim Bell, Nicole Barucci, Dennis Lee, Laurie J. Goodyear EWK, Morris F. White, and Gerald I. Shulman: Free Fatty Acid–Induced Insulin Resistance Is Associated With Activation of Protein Kinase C u and Alterations in the Insulin Signaling Cascade. Diabetes 1999, 48:1270–1274.
8. Carsten Schmitz-Peiffer CLB, Nicholas D. Oakes, Allan Watkinson, Donald J. Chisholm,, Edward W. Kraegen aTJB: Alterations in the expression and cellular localization of protein kinase C isozymes epsilon and theta are associated with insulin resistance in skeletal muscle of the high-fat-fed rat. Diabetes 1997, 46:169-178.
9. Kim JK, Fillmore JJ, Sunshine MJ, Albrecht B, Higashimori T, Kim D-W, Liu Z-X, Soos TJ, Cline GW, O’Brien WR, Littman DR and Shulman GI.: PKC-θ knockout mice are protected from fat-induced insulin resistance. Journal of Clinical Investigation 2004, 114:823-827.
10. Klein AM, Zaganjor E, Cobb MH: Chromatin-tethered MAPKs. Current Opinion in Cell Biology 2013, 25:272-277.
11. Philippe P. Roux and John Blenis: ERK and p38 MAPK-Activate Protein Kinases: a Family of Protein Kinases with Diverse Biological Functions. Microbiology and Molecular Biology Reviews 2004,68:320-344.
12. Green CJ, Macrae K, Fogarty S, Hardie DG, Sakamoto K, Hundal HS: Counter-modulation of fatty acid-induced pro-inflammatory nuclear factor kappaB signalling in rat skeletal muscle cells by AMP-activated protein kinase. Biochemical Journal 2011, 435:463-474.
13. Barnes PJ, Karin M: Nuclear Factor-κB — A Pivotal Transcription Factor in Chronic Inflammatory Diseases. New England Journal of Medicine 1997, 336:1066-1071.
14. Senftleben U, Cao Y, Xiao G, Greten FR, Krahn G, Bonizzi G, Chen Y, Hu Y, Fong A, Sun SC, Karin M: Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science 2001, 293:1495-1499.
15. Bing Tian and Allan R. Brasier: Identification of a Nuclear Factor Kappa B-dependent Gene Network. The Endocrine Society 2003, 1:95-130.
16. Rohl M, Pasparakis M, Baudler S, Baumgartl J, Gautam D, Huth M, De Lorenzi R, Krone W, Rajewsky K, Brüning JC: Conditional disruption of IκB kinase 2 fails to prevent obesity-induced insulin resistance. Journal of Clinical Investigation 2004, 113:474-481.
17. Yin M-J, Yamamoto Y, Gaynor RB.: The anti-inflammatory agents aspirin and salicylate inhibit the activity of IĸB kinase-β. Nature 1998,396:77-80.
18. Moshe Hacham RMW, Shmuel Argov, Shraga Segal, Ron N. Apte: Interleukin-6 and interleukin-10 are expressed in organs of normal young and old mice. European Cytokine Network 2004, 15:37-46.
19. Akira S HT, Taga T, Kishimoto T.: Biology of multifunctional cytokines: IL-6 and related molecules (IL-1 and TNF). Federation of American Societies for Experimental Biology l 1990, 11:2860-2867.
20. John S Yudkin, Meena Kumari, Steve E Humphries, and Vidya Mohamed-Ali: Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis 2000, 148:209-214.
21. Kristiansen OP M-PT: Interleukin-6 and diabetes: the good, the bad, or the indifferent? Diabetes 2005, 54:S114-S124.
22. Clark LA: How TNF was recognized as a key mechanism of disease. Cytokine Growth Factor Reviews 2007, 18:335-343.
23. J.C.Pickup MBM, G.D.Chusney, D.Butt: NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X.Diabetologia 1997, 40:1286-1292.
24. Hotamisligil GS AP, Caro JF, Atkinson RL, Spiegelman BM.:Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. the Journal of Clinical Investigation 1995, 95:2409-2415.
25. Yuan M, Konstantopoulos N, Lee J, Hansen L, Li ZW, Karin M, Shoelson SE: Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikk beta. Science 2001, 293:1673-1677.
26. K. Teoman Uysal SMW, Michael W. Marino Gokhan S. Hotamisligil: Protection fromobesityinduced insulin resistance in mice lacking TNF-α function. Nature 1997, 389:610-614.
27. Gokhan S. hotamisligil, D L Murray, L N Choy, and B M. Spiegelman: Tumor necrosis factor a inhibits signaling from the insulin receptor. Proceedings of the National Academy of Sciences of the United States of America 1994, 91:4854-4858.
28. Kadotani A TY, Hatakeyama H, Katagiri H, Kanzaki M.: Different impacts of saturated and unsaturated free fatty acids on COX-2 expression in C2C12 myotubes. the American Physiological Society 2009, 297.
29. Storlien LHH, Anthony J.; Else, Paul L.: Polyunsaturated fatty acids, membrane function and metabolic diseases such as diabetes and obesity. Current Opinion in Clinical Nutrition and Metabolic Care 1998, 1:559–563.
30. Moss GP: Nomenclature of steroids. International Union of Pure and Applied Chemistry 1989, 61:1783-1822.
31. Arthur A. Spector and Mark A. Yorek: Membrane lipid composition and cellular function. Journal of Lipid Research 1985, 26:1015-1035.
32. Riccardi G, Giacco R, Rivellese AA: Dietary fat, insulin sensitivity and the metabolic syndrome. Clinical Nutrition 2004, 23:447-456.
33. Leonard H Storlien, Arthur B Jenkins, Donald J Chisholm, Wendy S Pascoe, Sue Khouri and Edward W Kraegen: Influence of Dietary Fat Composition on Development of Insulin Resistance in Rats: Relationship to Muscle Triglyceride and ω-3 Fatty Acids in Muscle Phospholipid. Diabetes 1991, 40:280-289.
34. L.H.Storlien, D. A. Pan, A.D.Kriketos, and L. A.Baur: High Fat Diet-Induced Insulin Resistance. Annals New York Academy of Sciences 2006:82-90.
35. Lam YY, Hatzinikolas G, Weir JM, Janovska A, McAinch AJ, Game P, Meikle PJ, Wittert GA: Insulin-stimulated glucose uptake and pathways regulating energy metabolism in skeletal muscle cells: the effects of subcutaneous and visceral fat, and long-chain saturated, n-3 and n-6 polyunsaturated fatty acids. Biochim Biophys Acta- Molecular and Cell Biology of Lipids 2011, 1811:468-475.
36. Pascal P. H. Hommelberg JP, Ramon C. J. Langen,Annemie M.W.J. Schols, Mensink aRP: Fatty acid-induced NF-kB activation and insulin resistance in skeletal muscle are chain length dependent. American Journal of Physiology 2009, 296:E114-E120.
37. Kolapo M Ajuwon MES: Palmitate Activates the NF-kappaB Transcription Factor and Induces IL-6 and TNF-alpha Expression in 3T3-L1 Adipocytes. Journal of Nutrition 2005, 8:1841-1846.
38. Choi YJ, Choi SE, Ha ES, Kang Y, Han SJ, Kim DJ, Lee KW, Kim HJ: Involvement of visfatin in palmitate-induced upregulation of inflammatory cytokines in hepatocytes. Metabolism 2011, 60:1781-1789.
39. Yang L, Qian Z, Ji H, Yang R, Wang Y, Xi L, Sheng L, Zhao B, Zhang X: Inhibitory effect on protein kinase C theta by Crocetin attenuates palmitate-induced insulin insensitivity in 3T3-L1 adipocytes. European Journal of Pharmacology 2010, 642:47-55.
40. Cox MA: Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E2 and cytokines. World Journal of Gastroenterology 2009, 15:5549.
41.Giovannucci E, Goldin B.: The role of fat, fatty acids, and total energy intake in the etiology of human colon cancer. American Society for Clinical Nutrition 1997:1564S-1571S.
42. David L. Topping and Peter M. Clifton: Short-Chain Fatty Acids and Human Colonic Function: Roles of Resistant Starch and Nonstarch Polysaccharides. Physiological reviews 2001, 81:1031-1064.
43. Turkoglu S: Evaluation of genotoxic effects of sodium propionate, calcium propionate and potassium propionate on the root meristem cells of Allium cepa. Food and Chemical Toxicology 2008, 46:2035-2041.
44. Julia M. W. Wong R, w Russell de Souza, RD,w Cyril W. C. Kendall, PhD,w, Azadeh Emam M, and David J. A. Jenkins, MD: Colonic Health: Fermentation and Short Chain Fatty Acids. Journal of Clinical Gastroenterology 2006, 40:235-243.
45. Liu T, Li J, Liu Y, Xiao N, Suo H, Xie K, Yang C, Wu C: Short-chain fatty acids suppress lipopolysaccharide-induced production of nitric oxide and proinflammatory cytokines through inhibition of NF-kappaB pathway in RAW264.7 cells. Inflammation 2012, 35:1676-1684.
46. Gao Z, Yin J, Zhang J, Ward RE, Martin RJ, Lefevre M, Cefalu WT, Ye J: Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 2009, 58:1509-1517.
47. Abdul-Ghani MA: Contributions of Cell Dysfunction and Insulin Resistance to the Pathogenesis of Impaired Glucose Tolerance and Impaired Fasting Glucose. Diabetes Care 2006, 29:1130-1139.
48. Boden G: Role of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM. Diabetes Care 1997, 46:3-10.
49. G. Boden, G. I.Shulman: Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and β-cell dysfunction. European Journal of Clinical Investigation 2002, 32:14-23.
50. Goodarz Danaei, M.M.F., Yuan Lu, Gitanjali M Singh, Melanie J Cowan, Christopher J Paciorek, John K Lin, Farshad Farzadfar,Young-Ho Khang, Gretchen A Stevens, Mayuree Rao,Mohammed K Ali,Leanne M Riley, Carolyn A Robinson, Majid Ezzati: National, regional,and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet 2011, 378:31-40.
51. M. Bjornholm and J.R. Zierath: Insulin signal transduction in human skeletal muscle: identifying the defects in Type II diabetes. Biochemical Society Transactions 2005, 33:354-357.
52. Ole P. Kristiansen and Thomas Mandrup-Poulsen: Interleukin-6 and Diabetes. Diabetes 2005, 54:S114-S124.
53. Hyo-Jeong Kim TH, So-Young Park, Hyejeong Choi, Jianying Dong, Yoon-Jung Kim H-LN, You-Ree Cho,Gary Cline,Young-Bum Kim,and Jason K. Kim: Differential Effects of Interleukin-6 and -10 on Skeletal Muscle and Liver Insulin Action In Vivo. Diabetes 2004, 53:1060-1067.
54. Yongzhong Wei, K.Chen, Adam T. Whaley-Connell,Craig S. Stump, Jamal A. Ibdah, and James R.Sowers: Skeletal muscle insulin resistance: role of inflammatory cytokines and reactive oxygen species. the American Journal of Physiology Society 2007, 294:R673-R680.
55. Dongsheng Cai, M.Y., Daniel F Frantz, Peter A Melendez, Lone Hansen, Jongsoon Lee, and SE S: Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB. Nature Medicine 2005, 2:183–190.
56. Moussa A and Li Ji: AMPK in myocardial infarction and diabetes: the yin/yang effect. Acta Pharmaceutica Sinica B 2012, 2:368-378.
57. Salminen A and Kaarniranta K: AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Research Reviews 2012, 11:230-241.
58. Treebak JT, Glund S, Deshmukh A, Klein DK, Long YC, Jensen TE, Jorgensen SB, Viollet B, Andersson L, Neumann D, Wallimann T, Richter E A, Chibalin AV, Zierath JR, and Wojtaszewski JF.P.: AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits. Diabetes 2006, 55:2051-2058.
59. Shinya Yamaguchi HK, Sachihiko Ozawa, Yoko Nakamichi, Toshiaki Tanaka TS, Kazuto Takahashi, Katsuhiko Yoshimoto, Mica Ohara Imaizumi SN, and Hitoshi Ishida: Activators of AMP-activated protein kinase enhance GLUT4 translocation and its glucose transport activity in 3T3-L1 adipocytes. the American Physiological Society 2005, 289:E643-E649.
60. Eid HM, Martineau LC, Saleem A, Muhammad A, Vallerand D, Benhaddou-Andaloussi A, Nistor L, Afshar A, Arnason JT, Haddad PS: Stimulation of AMP-activated protein kinase and enhancement of basal glucose uptake in muscle cells by quercetin and quercetin glycosides, active principles of the antidiabetic medicinal plant Vaccinium vitis-idaea. Molecular Nutrition and Food Research 2010, 54:991-1003.
61. Shinya Yamaguchi HK, Sachihiko Ozawa,Yoko Nakamichi,, Toshiaki Tanaka TS, Kazuto Takahashi,Katsuhiko Yoshimoto,, Mica Ohara Imaizumi SN, and Hitoshi Ishida: Activators of AMP-activated protein kinase enhance GLUT4 translocation and its glucose transport activity in 3T3-L1 adipocytes. the American Physiological Society 2005, 289:E643-E649.
62. Kramer HF, Witczak CA, Taylor EB, Fujii N, Hirshman MF, Goodyear LJ: AS160 regulates insulin- and contraction-stimulated glucose uptake in mouse skeletal muscle. the Journal of Biological Chemistry 2006, 281:31478-31485.
63. Hakan K.R. Karlsson JRZ, Susan Kane, Anna Krook, Gustav E. Lienhard, and Harriet Wallberg-Henriksson: Insulin-Stimulated Phosphorylation of the Akt Substrate AS160 Is Impaired in Skeletal Muscle of Type 2 Diabetic Subjects. Diabetes Care 2005, 54:1692-1697.
64. Cohent DRAaP: Mechanism of activation and function of protein kinase B. Oncogenes and Cell Proliferation 1998:55-62.
65. Garofalo RS, Orena SJ, Rafidi K, Torchia AJ, Stock JL, Hildebrandt AL, Coskran T, Black SC, Brees DJ, Wicks JR, McNeish JD., and Coleman KG.: Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKBβ. Journal of Clinical Investigation 2003, 112:197-208.
66. Bae SS, Cho H, Mu J, Birnbaum MJ: Isoform-specific regulation of insulin-dependent glucose uptake by Akt/protein kinase B. the Journal of Biological Chemistry 2003, 278:49530-49536.
67. Carsten Schmitz-Peiffer DLC, and Trevor J. Biden: Ceramide Generation Is Sufficient to Account for the Inhibition of the Insulin-stimulated PKB Pathway in C2C12 Skeletal Muscle Cells Pretreated with Palmitate. the Journal of Biological Chemistry 1999, 274:24202-24210.
68. Wood IS, Trayhurn P: Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. British Journal of Nutrition 2007, 89:3.
69. Stuart CA, Wen G, Gustafson WC, Thompson EA: Comparison of GLUT1, GLUT3, and GLUT4 mRNA and the subcellular distribution of their proteins in normal human muscle. Metabolism 2000, 49:1604-1609.
70. Tsuchiya Y, Hatakeyama H, Emoto N, Wagatsuma F, Matsushita S, Kanzaki M: Palmitate-induced down-regulation of sortilin and impaired GLUT4 trafficking in C2C12 myotubes. the Journal of Biological Chemistry 2010, 285:34371-34381.
71. Michael D. Jensen MWH, Robert A. Rizza, Philip E. Cryer,and John M. Miles: Influence of Body Fat Distribution on Free Fatty Acid Metabolism in Obesity. Journal of Clinical Investigation 1989, 83:1168-1173.
72. Kharroubi I, Ladriere L, Cardozo AK, Dogusan Z, Cnop M, Eizirik DL: Free fatty acids and cytokines induce pancreatic beta-cell apoptosis by different mechanisms: role of nuclear factor-kappaB and endoplasmic reticulum stress. Endocrinology 2004, 145:5087-5096.
73. Michio shimabukuro Y-TZ, Moshe levi, and Roger H. Unger: Fatty acid-induced b cell apoptosis: A link between obesity and diabetes. Medical Science 1998, 95:2498-2502.
74. MD GB: Fatty acid—induced inflammation and insulin resistance in skeletal muscle and liver. Current Diabetes Reports 2006, 6:177-181.
75. Marco Aurélio Ramirez Vinolo HGR, William T. Festuccia,Amanda R. Crisma, Vitor S. Alves, Amanda R. Martins,Catia L. Amaral,Jarlei Fiamoncini,Sandro M. Hirabara,, Fabio T. Sato RAF, Gabriella Malheiros, Marinilce F. dos Santos,and Rui Curi: Tributyrin attenuates obesity-associated inflammation and insulin resistance in high-fat-fed mice. American Journal of Physiology - Endocrinology and Metabolism 2012, 303:E272–E282.
76. Amaral L, Hoppel C, Stephen A M: Effect of propionate on lipid metabolism in healthy human subjects. Falk Symposium 1993, 73:E2
77. T Venter C S, Vorster H H, Cummings J H. Effects of dietary propionate on carbohydrate and lipid metabolism in
healthy volunteers.the American Journal of Gastroenterology
1990, 85:549-553.
78. Bush RS, Milligan LP: Study of the mechanism of inhibition of ketogenesis by propionate in bovine liver. Canadian Journal of Animal Science 1971, 51:121-127.
79. J H Cummings, E W Pomare, W J Branch, C P Naylor, G T Macfarlane: Short chain fatty acids in human large intestine, portal, hepatic and venous blood. An International Journal of Gastroenterology and Hepatology 1987, 28: 1221-1227.
80. S. Lemosquet, E. Delamaire, H. Lapierre, J. W. Blum, and J. L. peyraud: Effects of glucose, propionic acid, and nonessential amino acids on glucose metabolism and milk yield in Holstein dairy cows.Journal of Dairy Science 2009, 92: 3244-3257.

QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔