Please use this identifier to cite or link to this item:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7830
Full metadata record
???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
---|---|---|
dc.contributor.advisor | 李宣書 | |
dc.contributor.author | Chiao-Yun Chien | en |
dc.contributor.author | 簡皎芸 | zh_TW |
dc.date.accessioned | 2021-05-19T17:55:11Z | - |
dc.date.available | 2022-02-08 | |
dc.date.available | 2021-05-19T17:55:11Z | - |
dc.date.copyright | 2017-02-08 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-09-21 | |
dc.identifier.citation | 1. Damasceno DC, Netto AO, Iessi IL, Gallego FQ, Corvino SB, Dallaqua B, Sinzato YK, Bueno A, Calderon IM, Rudge MV: Streptozotocin-induced diabetes models: pathophysiological mechanisms and fetal outcomes. Biomed Res Int 2014, 2014:819065.
2. Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, Raskin P, Zinman B, Diabetes C, Complications Trial/Epidemiology of Diabetes I, Complications Study Research G: Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005, 353:2643-2653. 3. Dor Y, Brown J, Martinez OI, Melton DA: Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 2004, 429:41-46. 4. Li W, Zhang H, Nie A, Ni Q, Li F, Ning G, Li X, Gu Y, Wang Q: mTORC1 pathway mediates beta cell compensatory proliferation in 60 % partial-pancreatectomy mice. Endocrine 2016, 53:117-128. 5. Wang G, Rajpurohit SK, Delaspre F, Walker SL, White DT, Ceasrine A, Kuruvilla R, Li RJ, Shim JS, Liu JO, et al: First quantitative high-throughput screen in zebrafish identifies novel pathways for increasing pancreatic beta-cell mass. Elife 2015, 4. 6. Berney T, Johnson PR: Donor pancreata: evolving approaches to organ allocation for whole pancreas versus islet transplantation. Transplantation 2010, 90:238-243. 7. Cramer JA, Pugh MJ: The influence of insulin use on glycemic control: How well do adults follow prescriptions for insulin? Diabetes Care 2005, 28:78-83. 8. Porat S, Weinberg-Corem N, Tornovsky-Babaey S, Schyr-Ben-Haroush R, Hija A, Stolovich-Rain M, Dadon D, Granot Z, Ben-Hur V, White P, et al: Control of pancreatic beta cell regeneration by glucose metabolism. Cell Metab 2011, 13:440-449. 9. Butler JM, Kobayashi H, Rafii S: Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors. Nat Rev Cancer 2010, 10:138-146. 10. Steiner DJ, Kim A, Miller K, Hara M: Pancreatic islet plasticity: interspecies comparison of islet architecture and composition. Islets 2010, 2:135-145. 11. Slack JM: Developmental biology of the pancreas. Development 1995, 121:1569-1580. 12. Pan FC, Wright C: Pancreas organogenesis: from bud to plexus to gland. Dev Dyn 2011, 240:530-565. 13. Assmann A, Hinault C, Kulkarni RN: Growth factor control of pancreatic islet regeneration and function. Pediatr Diabetes 2009, 10:14-32. 14. Bruni A, Gala-Lopez B, Pepper AR, Abualhassan NS, Shapiro AJ: Islet cell transplantation for the treatment of type 1 diabetes: recent advances and future challenges. Diabetes Metab Syndr Obes 2014, 7:211-223. 15. Qi M, Kinzer K, Danielson KK, Martellotto J, Barbaro B, Wang Y, Bui JT, Gaba RC, Knuttinen G, Garcia-Roca R, et al: Five-year follow-up of patients with type 1 diabetes transplanted with allogeneic islets: the UIC experience. Acta Diabetol 2014, 51:833-843. 16. Shapiro AM: Strategies toward single-donor islets of Langerhans transplantation. Curr Opin Organ Transplant 2011, 16:627-631. 17. Shapiro AM, Ricordi C, Hering BJ, Auchincloss H, Lindblad R, Robertson RP, Secchi A, Brendel MD, Berney T, Brennan DC, et al: International trial of the Edmonton protocol for islet transplantation. N Engl J Med 2006, 355:1318-1330. 18. Ludwig B, Rotem A, Schmid J, Weir GC, Colton CK, Brendel MD, Neufeld T, Block NL, Yavriyants K, Steffen A, et al: Improvement of islet function in a bioartificial pancreas by enhanced oxygen supply and growth hormone releasing hormone agonist. Proc Natl Acad Sci U S A 2012, 109:5022-5027. 19. Zhao T, Zhang ZN, Rong Z, Xu Y: Immunogenicity of induced pluripotent stem cells. Nature 2011, 474:212-215. 20. Araki R, Uda M, Hoki Y, Sunayama M, Nakamura M, Ando S, Sugiura M, Ideno H, Shimada A, Nifuji A, Abe M: Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells. Nature 2013, 494:100-104. 21. Vegas AJ, Veiseh O, Gurtler M, Millman JR, Pagliuca FW, Bader AR, Doloff JC, Li J, Chen M, Olejnik K, et al: Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. Nat Med 2016, 22:306-311. 22. Hua H, Shang L, Martinez H, Freeby M, Gallagher MP, Ludwig T, Deng L, Greenberg E, Leduc C, Chung WK, et al: iPSC-derived beta cells model diabetes due to glucokinase deficiency. J Clin Invest 2013, 123:3146-3153. 23. Pagliuca FW, Millman JR, Gurtler M, Segel M, Van Dervort A, Ryu JH, Peterson QP, Greiner D, Melton DA: Generation of functional human pancreatic beta cells in vitro. Cell 2014, 159:428-439. 24. Rezania A, Bruin JE, Arora P, Rubin A, Batushansky I, Asadi A, O'Dwyer S, Quiskamp N, Mojibian M, Albrecht T, et al: Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat Biotechnol 2014, 32:1121-1133. 25. Robinton DA, Daley GQ: The promise of induced pluripotent stem cells in research and therapy. Nature 2012, 481:295-305. 26. Bendich A, Olson JA: Biological actions of carotenoids. FASEB J 1989, 3:1927-1932. 27. Napoli JL: Interactions of retinoid binding proteins and enzymes in retinoid metabolism. Biochim Biophys Acta 1999, 1440:139-162. 28. Wolbach SB, Howe PR: Tissue Changes Following Deprivation of Fat-Soluble a Vitamin. J Exp Med 1925, 42:753-777. 29. Prieur DJ, Fenstermacher JD, Guarino AM: A choroid plexus papilloma in an elasmobranch (Squalus acanthias). J Natl Cancer Inst 1976, 56:1207-1209. 30. Coombs CC, Tavakkoli M, Tallman MS: Acute promyelocytic leukemia: where did we start, where are we now, and the future. Blood Cancer J 2015, 5:e304. 31. Brun PJ, Yang KJ, Lee SA, Yuen JJ, Blaner WS: Retinoids: Potent regulators of metabolism. Biofactors 2013, 39:151-163. 32. Villarroya F, Iglesias R, Giralt M: Retinoids and retinoid receptors in the control of energy balance: novel pharmacological strategies in obesity and diabetes. Curr Med Chem 2004, 11:795-805. 33. Ross AC CB, Cousins RJ, Tucker KL, Ziegler TR: Modern Nutrition in Health and Diseases. 11th edition edn. Philadelphia: Wolters Kluwer; 2012. 34. Noy N, Xu ZJ: Interactions of retinol with binding proteins: implications for the mechanism of uptake by cells. Biochemistry 1990, 29:3878-3883. 35. Kawaguchi R, Yu J, Honda J, Hu J, Whitelegge J, Ping P, Wiita P, Bok D, Sun H: A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A. Science 2007, 315:820-825. 36. Moise AR, Noy N, Palczewski K, Blaner WS: Delivery of retinoid-based therapies to target tissues. Biochemistry 2007, 46:4449-4458. 37. Theodosiou M, Laudet V, Schubert M: From carrot to clinic: an overview of the retinoic acid signaling pathway. Cell Mol Life Sci 2010, 67:1423-1445. 38. Duester G, Mic FA, Molotkov A: Cytosolic retinoid dehydrogenases govern ubiquitous metabolism of retinol to retinaldehyde followed by tissue-specific metabolism to retinoic acid. Chem Biol Interact 2003, 143-144:201-210. 39. Pares X, Farres J, Kedishvili N, Duester G: Medium- and short-chain dehydrogenase/reductase gene and protein families : Medium-chain and short-chain dehydrogenases/reductases in retinoid metabolism. Cell Mol Life Sci 2008, 65:3936-3949. 40. Napoli JL: Retinoic acid biosynthesis and metabolism. FASEB J 1996, 10:993-1001. 41. Lin M, Zhang M, Abraham M, Smith SM, Napoli JL: Mouse retinal dehydrogenase 4 (RALDH4), molecular cloning, cellular expression, and activity in 9-cis-retinoic acid biosynthesis in intact cells. J Biol Chem 2003, 278:9856-9861. 42. Bhat PV, Labrecque J, Boutin JM, Lacroix A, Yoshida A: Cloning of a cDNA encoding rat aldehyde dehydrogenase with high activity for retinal oxidation. Gene 1995, 166:303-306. 43. Molotkov A, Duester G: Genetic evidence that retinaldehyde dehydrogenase Raldh1 (Aldh1a1) functions downstream of alcohol dehydrogenase Adh1 in metabolism of retinol to retinoic acid. J Biol Chem 2003, 278:36085-36090. 44. Elizondo G, Corchero J, Sterneck E, Gonzalez FJ: Feedback inhibition of the retinaldehyde dehydrogenase gene ALDH1 by retinoic acid through retinoic acid receptor alpha and CCAAT/enhancer-binding protein beta. J Biol Chem 2000, 275:39747-39753. 45. Elizondo G, Medina-Diaz IM, Cruz R, Gonzalez FJ, Vega L: Retinoic acid modulates retinaldehyde dehydrogenase 1 gene expression through the induction of GADD153-C/EBPbeta interaction. Biochem Pharmacol 2009, 77:248-257. 46. Fujiwara K, Kikuchi M, Horiguchi K, Kusumoto K, Kouki T, Kawanishi K, Yashiro T: Estrogen receptor alpha regulates retinaldehyde dehydrogenase 1 expression in rat anterior pituitary cells. Endocr J 2009, 56:963-973. 47. Fujiwara K, Maekawa F, Kikuchi M, Takigami S, Yada T, Yashiro T: Expression of retinaldehyde dehydrogenase (RALDH)2 and RALDH3 but not RALDH1 in the developing anterior pituitary glands of rats. Cell Tissue Res 2007, 328:129-135. 48. Maden M: Retinoid signalling in the development of the central nervous system. Nat Rev Neurosci 2002, 3:843-853. 49. Malpel S, Mendelsohn C, Cardoso WV: Regulation of retinoic acid signaling during lung morphogenesis. Development 2000, 127:3057-3067. 50. Mendelsohn C, Batourina E, Fung S, Gilbert T, Dodd J: Stromal cells mediate retinoid-dependent functions essential for renal development. Development 1999, 126:1139-1148. 51. Plateroti M, Freund JN, Leberquier C, Kedinger M: Mesenchyme-mediated effects of retinoic acid during rat intestinal development. J Cell Sci 1997, 110 ( Pt 10):1227-1238. 52. Altucci L, Gronemeyer H: The promise of retinoids to fight against cancer. Nat Rev Cancer 2001, 1:181-193. 53. Dolle P, Ruberte E, Leroy P, Morriss-Kay G, Chambon P: Retinoic acid receptors and cellular retinoid binding proteins. I. A systematic study of their differential pattern of transcription during mouse organogenesis. Development 1990, 110:1133-1151. 54. Mangelsdorf DJ, Borgmeyer U, Heyman RA, Zhou JY, Ong ES, Oro AE, Kakizuka A, Evans RM: Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Dev 1992, 6:329-344. 55. Smith JE, Milch PO, Muto Y, Goodman DS: The plasma transport and metabolism of retinoic acid in the rat. Biochem J 1973, 132:821-827. 56. Chambon P: A decade of molecular biology of retinoic acid receptors. FASEB J 1996, 10:940-954. 57. Davidovici BB, Tuzun Y, Wolf R: Retinoid receptors. Dermatol Clin 2007, 25:525-530, viii. 58. Blomhoff R, Blomhoff HK: Overview of retinoid metabolism and function. J Neurobiol 2006, 66:606-630. 59. Dolle P, Ruberte E, Kastner P, Petkovich M, Stoner CM, Gudas LJ, Chambon P: Differential expression of genes encoding alpha, beta and gamma retinoic acid receptors and CRABP in the developing limbs of the mouse. Nature 1989, 342:702-705. 60. Ruberte E, Dolle P, Chambon P, Morriss-Kay G: Retinoic acid receptors and cellular retinoid binding proteins. II. Their differential pattern of transcription during early morphogenesis in mouse embryos. . Development 1991, 111:45-60. 61. Ruberte E, Friederich V, Chambon P, Morriss-Kay G: Retinoic acid receptors and cellular retinoid binding proteins. III. Their differential transcript distribution during mouse nervous system development. Development 1993, 118:267-282. 62. Mark M, Ghyselinck NB, Chambon P: Function of retinoic acid receptors during embryonic development. Nucl Recept Signal 2009, 7:e002. 63. Krezel W, Ghyselinck N, Samad TA, Dupe V, Kastner P, Borrelli E, Chambon P: Impaired locomotion and dopamine signaling in retinoid receptor mutant mice. Science 1998, 279:863-867. 64. Liao WL, Tsai HC, Wang HF, Chang J, Lu KM, Wu HL, Lee YC, Tsai TF, Takahashi H, Wagner M, et al: Modular patterning of structure and function of the striatum by retinoid receptor signaling. Proc Natl Acad Sci U S A 2008, 105:6765-6770. 65. Krust A, Kastner P, Petkovich M, Zelent A, Chambon P: A third human retinoic acid receptor, hRAR-gamma. Proc Natl Acad Sci U S A 1989, 86:5310-5314. 66. Zelent A, Krust A, Petkovich M, Kastner P, Chambon P: Cloning of murine alpha and beta retinoic acid receptors and a novel receptor gamma predominantly expressed in skin. Nature 1989, 339:714-717. 67. Rochette-Egly C, Oulad-Abdelghani M, Staub A, Pfister V, Scheuer I, Chambon P, Gaub MP: Phosphorylation of the retinoic acid receptor-alpha by protein kinase A. Mol Endocrinol 1995, 9:860-871. 68. Rochette-Egly C, Adam S, Rossignol M, Egly JM, Chambon P: Stimulation of RAR alpha activation function AF-1 through binding to the general transcription factor TFIIH and phosphorylation by CDK7. Cell 1997, 90:97-107. 69. Delmotte MH, Tahayato A, Formstecher P, Lefebvre P: Serine 157, a retinoic acid receptor alpha residue phosphorylated by protein kinase C in vitro, is involved in RXR.RARalpha heterodimerization and transcriptional activity. J Biol Chem 1999, 274:38225-38231. 70. Srinivas H, Xia D, Moore NL, Uray IP, Kim H, Ma L, Weigel NL, Brown PH, Kurie JM: Akt phosphorylates and suppresses the transactivation of retinoic acid receptor alpha. Biochem J 2006, 395:653-662. 71. Lee HY, Suh YA, Robinson MJ, Clifford JL, Hong WK, Woodgett JR, Cobb MH, Mangelsdorf DJ, Kurie JM: Stress pathway activation induces phosphorylation of retinoid X receptor. J Biol Chem 2000, 275:32193-32199. 72. Matsushima-Nishiwaki R, Okuno M, Adachi S, Sano T, Akita K, Moriwaki H, Friedman SL, Kojima S: Phosphorylation of retinoid X receptor alpha at serine 260 impairs its metabolism and function in human hepatocellular carcinoma. Cancer Res 2001, 61:7675-7682. 73. Yamazaki K, Shimizu M, Okuno M, Matsushima-Nishiwaki R, Kanemura N, Araki H, Tsurumi H, Kojima S, Weinstein IB, Moriwaki H: Synergistic effects of RXR alpha and PPAR gamma ligands to inhibit growth in human colon cancer cells--phosphorylated RXR alpha is a critical target for colon cancer management. Gut 2007, 56:1557-1563. 74. Kam RK, Deng Y, Chen Y, Zhao H: Retinoic acid synthesis and functions in early embryonic development. Cell Biosci 2012, 2:11. 75. Das BC, Thapa P, Karki R, Das S, Mahapatra S, Liu TC, Torregroza I, Wallace DP, Kambhampati S, Van Veldhuizen P, et al: Retinoic acid signaling pathways in development and diseases. Bioorg Med Chem 2014, 22:673-683. 76. Connolly RM, Nguyen NK, Sukumar S: Molecular pathways: current role and future directions of the retinoic acid pathway in cancer prevention and treatment. Clin Cancer Res 2013, 19:1651-1659. 77. Zhao S, Li R, Li Y, Chen W, Zhang Y, Chen G: Roles of vitamin A status and retinoids in glucose and fatty acid metabolism. Biochem Cell Biol 2012, 90:142-152. 78. Mongan NP, Gudas LJ: Diverse actions of retinoid receptors in cancer prevention and treatment. Differentiation 2007, 75:853-870. 79. Basu TK, Tze WJ, Leichter J: Serum vitamin A and retinol-binding protein in patients with insulin-dependent diabetes mellitus. Am J Clin Nutr 1989, 50:329-331. 80. Tuitoek PJ, Ziari S, Tsin AT, Rajotte RV, Suh M, Basu TK: Streptozotocin-induced diabetes in rats is associated with impaired metabolic availability of vitamin A (retinol). Br J Nutr 1996, 75:615-622. 81. Lu J, Dixon WT, Tsin AT, Basu TK: The metabolic availability of vitamin A is decreased at the onset of diabetes in BB rats. J Nutr 2000, 130:1958-1962. 82. Krill D, O'Leary L, Koehler AN, Kramer MK, Warty V, Wagner MA, Dorman JS: Association of retinol binding protein in multiple-case families with insulin-dependent diabetes. Hum Biol 1997, 69:89-96. 83. Chen M, Thomson AB, Tsin AT, Basu TK: The hepatic retinyl ester hydrolase activity is depressed at the onset of diabetes in BB rats. Br J Nutr 2003, 89:231-238. 84. Dubrey SW, Beetham R, Miles J, Noble MI, Rowe R, Leslie RD: Increased urinary albumin and retinol-binding protein in type I diabetes. A study of identical twins. Diabetes Care 1997, 20:84-89. 85. Trasino SE, Benoit YD, Gudas LJ: Vitamin A deficiency causes hyperglycemia and loss of pancreatic beta-cell mass. J Biol Chem 2015, 290:1456-1473. 86. Matthews KA, Rhoten WB, Driscoll HK, Chertow BS: Vitamin A deficiency impairs fetal islet development and causes subsequent glucose intolerance in adult rats. J Nutr 2004, 134:1958-1963. 87. Zunino SJ, Storms DH, Stephensen CB: Diets rich in polyphenols and vitamin A inhibit the development of type I autoimmune diabetes in nonobese diabetic mice. J Nutr 2007, 137:1216-1221. 88. Chertow BS, Baker GR: The effects of vitamin A on insulin release and glucose oxidation in isolated rat islets. Endocrinology 1978, 103:1562-1572. 89. Chertow BS, Blaner WS, Baranetsky NG, Sivitz WI, Cordle MB, Thompson D, Meda P: Effects of vitamin A deficiency and repletion on rat insulin secretion in vivo and in vitro from isolated islets. J Clin Invest 1987, 79:163-169. 90. Chertow BS, Goking NQ, Driscoll HK, Primerano DA, Matthews KA: Effects of all-trans-retinoic acid (ATRA) and retinoic acid receptor (RAR) expression on secretion, growth, and apoptosis of insulin-secreting RINm5F cells. Pancreas 1997, 15:122-131. 91. Blumentrath J, Neye H, Verspohl EJ: Effects of retinoids and thiazolidinediones on proliferation, insulin release, insulin mRNA, GLUT 2 transporter protein and mRNA of INS-1 cells. Cell Biochem Funct 2001, 19:159-169. 92. West KP, Jr., Christian P, Labrique AB, Rashid M, Shamim AA, Klemm RD, Massie AB, Mehra S, Schulze KJ, Ali H, et al: Effects of vitamin A or beta carotene supplementation on pregnancy-related mortality and infant mortality in rural Bangladesh: a cluster randomized trial. JAMA 2011, 305:1986-1995. 93. Lakshmy R: Metabolic syndrome: role of maternal undernutrition and fetal programming. Rev Endocr Metab Disord 2013, 14:229-240. 94. Clagett-Dame M, DeLuca HF: The role of vitamin A in mammalian reproduction and embryonic development. Annu Rev Nutr 2002, 22:347-381. 95. Li N, Sun S, Wang D, Yao P, Yang X, Yan H, Du Y, Ying C, Liu L: Suppression of retinoic acid receptors may contribute to embryonic skeleton hypoplasia in maternal rats with chronic vitamin A deficiency. J Nutr Biochem 2010, 21:710-716. 96. Stafford D, Prince VE: Retinoic acid signaling is required for a critical early step in zebrafish pancreatic development. Curr Biol 2002, 12:1215-1220. 97. Molotkov A, Molotkova N, Duester G: Retinoic acid generated by Raldh2 in mesoderm is required for mouse dorsal endodermal pancreas development. Dev Dyn 2005, 232:950-957. 98. Martin M, Gallego-Llamas J, Ribes V, Kedinger M, Niederreither K, Chambon P, Dolle P, Gradwohl G: Dorsal pancreas agenesis in retinoic acid-deficient Raldh2 mutant mice. Dev Biol 2005, 284:399-411. 99. Ostrom M, Loffler KA, Edfalk S, Selander L, Dahl U, Ricordi C, Jeon J, Correa-Medina M, Diez J, Edlund H: Retinoic acid promotes the generation of pancreatic endocrine progenitor cells and their further differentiation into beta-cells. PLoS One 2008, 3:e2841. 100. Chen Y, Pan FC, Brandes N, Afelik S, Solter M, Pieler T: Retinoic acid signaling is essential for pancreas development and promotes endocrine at the expense of exocrine cell differentiation in Xenopus. Dev Biol 2004, 271:144-160. 101. Huang W, Wang G, Delaspre F, Vitery Mdel C, Beer RL, Parsons MJ: Retinoic acid plays an evolutionarily conserved and biphasic role in pancreas development. Dev Biol 2014, 394:83-93. 102. Penny C, Kramer B: The effect of retinoic acid on the proportion of insulin cells in the developing chick pancreas. In Vitro Cell Dev Biol Anim 2000, 36:14-18. 103. Cabrera-Valladares G, German MS, Matschinsky FM, Wang J, Fernandez-Mejia C: Effect of retinoic acid on glucokinase activity and gene expression and on insulin secretion in primary cultures of pancreatic islets. Endocrinology 1999, 140:3091-3096. 104. Stafford D, Hornbruch A, Mueller PR, Prince VE: A conserved role for retinoid signaling in vertebrate pancreas development. Dev Genes Evol 2004, 214:432-441. 105. Kobayashi H, Spilde TL, Bhatia AM, Buckingham RB, Hembree MJ, Prasadan K, Preuett BL, Imamura M, Gittes GK: Retinoid signaling controls mouse pancreatic exocrine lineage selection through epithelial-mesenchymal interactions. Gastroenterology 2002, 123:1331-1340. 106. Perez RJ, Benoit YD, Gudas LJ: Deletion of retinoic acid receptor beta (RARbeta) impairs pancreatic endocrine differentiation. Exp Cell Res 2013, 319:2196-2204. 107. Kadison A, Kim J, Maldonado T, Crisera C, Prasadan K, Manna P, Preuett B, Hembree M, Longaker M, Gittes G: Retinoid signaling directs secondary lineage selection in pancreatic organogenesis. J Pediatr Surg 2001, 36:1150-1156. 108. Shen CN, Marguerie A, Chien CY, Dickson C, Slack JM, Tosh D: All-trans retinoic acid suppresses exocrine differentiation and branching morphogenesis in the embryonic pancreas. Differentiation 2007, 75:62-74. 109. Hynes RO: The extracellular matrix: not just pretty fibrils. Science 2009, 326:1216-1219. 110. Bonnans C, Chou J, Werb Z: Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol 2014, 15:786-801. 111. Tanzer ML: Current concepts of extracellular matrix. J Orthop Sci 2006, 11:326-331. 112. Frantz C, Stewart KM, Weaver VM: The extracellular matrix at a glance. J Cell Sci 2010, 123:4195-4200. 113. Kragl M, Lammert E: Basement membrane in pancreatic islet function. Adv Exp Med Biol 2010, 654:217-234. 114. Pinkse GG, Bouwman WP, Jiawan-Lalai R, Terpstra OT, Bruijn JA, de Heer E: Integrin signaling via RGD peptides and anti-beta1 antibodies confers resistance to apoptosis in islets of Langerhans. Diabetes 2006, 55:312-317. 115. Wang RN, Paraskevas S, Rosenberg L: Characterization of integrin expression in islets isolated from hamster, canine, porcine, and human pancreas. J Histochem Cytochem 1999, 47:499-506. 116. Behrens DT, Villone D, Koch M, Brunner G, Sorokin L, Robenek H, Bruckner-Tuderman L, Bruckner P, Hansen U: The epidermal basement membrane is a composite of separate laminin- or collagen IV-containing networks connected by aggregated perlecan, but not by nidogens. J Biol Chem 2012, 287:18700-18709. 117. Fox JW, Mayer U, Nischt R, Aumailley M, Reinhardt D, Wiedemann H, Mann K, Timpl R, Krieg T, Engel J, et al.: Recombinant nidogen consists of three globular domains and mediates binding of laminin to collagen type IV. EMBO J 1991, 10:3137-3146. 118. Mayer U, Kohfeldt E, Timpl R: Structural and genetic analysis of laminin-nidogen interaction. Ann N Y Acad Sci 1998, 857:130-142. 119. Mayer U, Mann K, Timpl R, Murphy G: Sites of nidogen cleavage by proteases involved in tissue homeostasis and remodelling. Eur J Biochem 1993, 217:877-884. 120. Aumailley M, Battaglia C, Mayer U, Reinhardt D, Nischt R, Timpl R, Fox JW: Nidogen mediates the formation of ternary complexes of basement membrane components. Kidney Int 1993, 43:7-12. 121. Durbeej M: Laminins. Cell Tissue Res 2010, 339:259-268. 122. Li S, Liquari P, McKee KK, Harrison D, Patel R, Lee S, Yurchenco PD: Laminin-sulfatide binding initiates basement membrane assembly and enables receptor signaling in Schwann cells and fibroblasts. J Cell Biol 2005, 169:179-189. 123. Bonner-Weir S, Orci L: New perspectives on the microvasculature of the islets of Langerhans in the rat. Diabetes 1982, 31:883-889. 124. Olsson R, Carlsson PO: The pancreatic islet endothelial cell: emerging roles in islet function and disease. Int J Biochem Cell Biol 2006, 38:492-497. 125. Nikolova G, Strilic B, Lammert E: The vascular niche and its basement membrane. Trends Cell Biol 2007, 17:19-25. 126. Virtanen I, Banerjee M, Palgi J, Korsgren O, Lukinius A, Thornell LE, Kikkawa Y, Sekiguchi K, Hukkanen M, Konttinen YT, Otonkoski T: Blood vessels of human islets of Langerhans are surrounded by a double basement membrane. Diabetologia 2008, 51:1181-1191. 127. Korpos E, Kadri N, Kappelhoff R, Wegner J, Overall CM, Weber E, Holmberg D, Cardell S, Sorokin L: The peri-islet basement membrane, a barrier to infiltrating leukocytes in type 1 diabetes in mouse and human. Diabetes 2013, 62:531-542. 128. Otonkoski T, Banerjee M, Korsgren O, Thornell LE, Virtanen I: Unique basement membrane structure of human pancreatic islets: implications for beta-cell growth and differentiation. Diabetes Obes Metab 2008, 10 Suppl 4:119-127. 129. Nikolova G, Jabs N, Konstantinova I, Domogatskaya A, Tryggvason K, Sorokin L, Fassler R, Gu G, Gerber HP, Ferrara N, et al: The vascular basement membrane: a niche for insulin gene expression and Beta cell proliferation. Dev Cell 2006, 10:397-405. 130. Bosco D, Meda P, Halban PA, Rouiller DG: Importance of cell-matrix interactions in rat islet beta-cell secretion in vitro: role of alpha6beta1 integrin. Diabetes 2000, 49:233-243. 131. Bosco DA, Kern D: Catalysis and binding of cyclophilin A with different HIV-1 capsid constructs. Biochemistry 2004, 43:6110-6119. 132. Hammar E, Tomas A, Bosco D, Halban PA: Role of the Rho-ROCK (Rho-associated kinase) signaling pathway in the regulation of pancreatic beta-cell function. Endocrinology 2009, 150:2072-2079. 133. Hammar EB, Irminger JC, Rickenbach K, Parnaud G, Ribaux P, Bosco D, Rouiller DG, Halban PA: Activation of NF-kappaB by extracellular matrix is involved in spreading and glucose-stimulated insulin secretion of pancreatic beta cells. J Biol Chem 2005, 280:30630-30637. 134. Parnaud G, Hammar E, Rouiller DG, Armanet M, Halban PA, Bosco D: Blockade of beta1 integrin-laminin-5 interaction affects spreading and insulin secretion of rat beta-cells attached on extracellular matrix. Diabetes 2006, 55:1413-1420. 135. Miyazaki J, Araki K, Yamato E, Ikegami H, Asano T, Shibasaki Y, Oka Y, Yamamura K: Establishment of a pancreatic beta cell line that retains glucose-inducible insulin secretion: special reference to expression of glucose transporter isoforms. Endocrinology 1990, 127:126-132. 136. Brissova M, Shostak A, Shiota M, Wiebe PO, Poffenberger G, Kantz J, Chen Z, Carr C, Jerome WG, Chen J, et al: Pancreatic islet production of vascular endothelial growth factor--a is essential for islet vascularization, revascularization, and function. Diabetes 2006, 55:2974-2985. 137. Nyman LR, Wells KS, Head WS, McCaughey M, Ford E, Brissova M, Piston DW, Powers AC: Real-time, multidimensional in vivo imaging used to investigate blood flow in mouse pancreatic islets. J Clin Invest 2008, 118:3790-3797. 138. Kamba T, Tam BY, Hashizume H, Haskell A, Sennino B, Mancuso MR, Norberg SM, O'Brien SM, Davis RB, Gowen LC, et al: VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circ Physiol 2006, 290:H560-576. 139. El-Gohary Y, Sims-Lucas S, Lath N, Tulachan S, Guo P, Xiao X, Welsh C, Paredes J, Wiersch J, Prasadan K, et al: Three-dimensional analysis of the islet vasculature. Anat Rec (Hoboken) 2012, 295:1473-1481. 140. Cai Q, Brissova M, Reinert RB, Pan FC, Brahmachary P, Jeansson M, Shostak A, Radhika A, Poffenberger G, Quaggin SE, et al: Enhanced expression of VEGF-A in beta cells increases endothelial cell number but impairs islet morphogenesis and beta cell proliferation. Dev Biol 2012, 367:40-54. 141. Magenheim J, Ilovich O, Lazarus A, Klochendler A, Ziv O, Werman R, Hija A, Cleaver O, Mishani E, Keshet E, Dor Y: Blood vessels restrain pancreas branching, differentiation and growth. Development 2011, 138:4743-4752. 142. Reinert RB, Cai Q, Hong JY, Plank JL, Aamodt K, Prasad N, Aramandla R, Dai C, Levy SE, Pozzi A, et al: Vascular endothelial growth factor coordinates islet innervation via vascular scaffolding. Development 2014, 141:1480-1491. 143. Sand FW, Hornblad A, Johansson JK, Loren C, Edsbagge J, Stahlberg A, Magenheim J, Ilovich O, Mishani E, Dor Y, et al: Growth-limiting role of endothelial cells in endoderm development. Dev Biol 2011, 352:267-277. 144. Christofori G, Naik P, Hanahan D: Vascular endothelial growth factor and its receptors, flt-1 and flk-1, are expressed in normal pancreatic islets and throughout islet cell tumorigenesis. Mol Endocrinol 1995, 9:1760-1770. 145. Inoue M, Hager JH, Ferrara N, Gerber HP, Hanahan D: VEGF-A has a critical, nonredundant role in angiogenic switching and pancreatic beta cell carcinogenesis. Cancer Cell 2002, 1:193-202. 146. Lammert E, Gu G, McLaughlin M, Brown D, Brekken R, Murtaugh LC, Gerber HP, Ferrara N, Melton DA: Role of VEGF-A in vascularization of pancreatic islets. Curr Biol 2003, 13:1070-1074. 147. Cleaver O, Melton DA: Endothelial signaling during development. Nat Med 2003, 9:661-668. 148. Lammert E, Cleaver O, Melton D: Induction of pancreatic differentiation by signals from blood vessels. Science 2001, 294:564-567. 149. Cleaver O, Dor Y: Vascular instruction of pancreas development. Development 2012, 139:2833-2843. 150. Iwashita N, Uchida T, Choi JB, Azuma K, Ogihara T, Ferrara N, Gerber H, Kawamori R, Inoue M, Watada H: Impaired insulin secretion in vivo but enhanced insulin secretion from isolated islets in pancreatic beta cell-specific vascular endothelial growth factor-A knock-out mice. Diabetologia 2007, 50:380-389. 151. Agudo J, Ayuso E, Jimenez V, Casellas A, Mallol C, Salavert A, Tafuro S, Obach M, Ruzo A, Moya M, et al: Vascular endothelial growth factor-mediated islet hypervascularization and inflammation contribute to progressive reduction of beta-cell mass. Diabetes 2012, 61:2851-2861. 152. Ferrara N, Gerber HP, LeCouter J: The biology of VEGF and its receptors. Nat Med 2003, 9:669-676. 153. Carmeliet P, Jain RK: Molecular mechanisms and clinical applications of angiogenesis. Nature 2011, 473:298-307. 154. Darland DC, Cain JT, Berosik MA, Saint-Geniez M, Odens PW, Schaubhut GJ, Frisch S, Stemmer-Rachamimov A, Darland T, D'Amore PA: Vascular endothelial growth factor (VEGF) isoform regulation of early forebrain development. Dev Biol 2011, 358:9-22. 155. Wada T, Haigh JJ, Ema M, Hitoshi S, Chaddah R, Rossant J, Nagy A, van der Kooy D: Vascular endothelial growth factor directly inhibits primitive neural stem cell survival but promotes definitive neural stem cell survival. J Neurosci 2006, 26:6803-6812. 156. Pugh CW, Ratcliffe PJ: Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med 2003, 9:677-684. 157. Rieck S, Kaestner KH: Expansion of beta-cell mass in response to pregnancy. Trends Endocrinol Metab 2010, 21:151-158. 158. Kisanuki YY, Hammer RE, Miyazaki J, Williams SC, Richardson JA, Yanagisawa M: Tie2-Cre transgenic mice: a new model for endothelial cell-lineage analysis in vivo. Dev Biol 2001, 230:230-242. 159. Andersson A: Isolated mouse pancreatic islets in culture: effects of serum and different culture media on the insulin production of the islets. Diabetologia 1978, 14:397-404. 160. Zhang N, Richter A, Suriawinata J, Harbaran S, Altomonte J, Cong L, Zhang H, Song K, Meseck M, Bromberg J, Dong H: Elevated vascular endothelial growth factor production in islets improves islet graft vascularization. Diabetes 2004, 53:963-970. 161. Olsson R, Carlsson PO: Better vascular engraftment and function in pancreatic islets transplanted without prior culture. Diabetologia 2005, 48:469-476. 162. Yoshitomi H, Zaret KS: Endothelial cell interactions initiate dorsal pancreas development by selectively inducing the transcription factor Ptf1a. Development 2004, 131:807-817. 163. Jacquemin P, Yoshitomi H, Kashima Y, Rousseau GG, Lemaigre FP, Zaret KS: An endothelial-mesenchymal relay pathway regulates early phases of pancreas development. Dev Biol 2006, 290:189-199. 164. Novak A, Guo C, Yang W, Nagy A, Lobe CG: Z/EG, a double reporter mouse line that expresses enhanced green fluorescent protein upon Cre-mediated excision. Genesis 2000, 28:147-155. 165. Percival AC, Slack JM: Analysis of pancreatic development using a cell lineage label. Exp Cell Res 1999, 247:123-132. 166. Thowfeequ S, Ralphs KL, Yu WY, Slack JM, Tosh D: Betacellulin inhibits amylase and glucagon production and promotes beta cell differentiation in mouse embryonic pancreas. Diabetologia 20 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7830 | - |
dc.description.abstract | 糖尿病是一種代謝異常疾病,主要原因是由於體內胰島素缺乏或胰島素阻抗性而所造成血糖高於標準值。其中第一型糖尿病(胰島素依賴型糖尿病)的病人因為體內胰島素缺乏,所以可透過胰島素注射治療,但是要達到長期有效的調控及維持血糖,可能的治療方法為胰島移植。然而,胰島移植的兩項瓶頸是胰島來源的絕對缺乏,以及移植後的胰島存活及功能不佳,使得此項治療還未能廣泛應用在治療第一型糖尿病的患者。本篇論文的主要目標以胰島移植來治療糖尿病為基礎下探討可能的改善方式,在研究的第一個部分,我們首先分析並發現人體必需的營養素維他命A在胚胎發育時期是重要影響因子。我們進一步發現全反式維甲酸, 維他命A酸代謝活性產物,對於胰臟發育扮演重要角色。因此,我們透過探討母體維生素A缺乏時如何影響胎兒時期的胰島細胞發育,發現全反式維甲酸藉由調控胰島細胞自行分泌血管內皮生長因子促成胰島內微血管網的生成。根據這樣的結果,我們進一步探討是否全反式維甲酸能夠用於改善糖尿病治療,結果顯示全反式維甲酸能夠逐漸透過增加β細胞的數量,以及修復血管層粘連蛋白的表現來改善糖尿病小鼠的血糖控制,主因是全反式維甲酸能藉由調控胰島細胞自行分泌血管內皮生長因子促成糖尿病鼠胰島內微血管網的生成、血管層粘連蛋白的表現和β細胞增生。重要的是發現全反式維甲酸也可以增進移植胰島內微血管網的生成細及胰島素分泌功能,而能夠有效改善糖尿病小鼠的高血糖症狀。而在研究的第二個部分,我們試著在三維的細胞培養系統來重新編程肝臟細胞成為表現Sox9的肝前驅細胞,這些表現Sox9的肝前驅細胞能在聚乙烯醇(Polyvinyl alcohol, PVA)受質上形成球體狀的結構;進一步結合表現Pdx1, Ngn3 與 MafA三個轉錄因子將其重新編程成為製造胰島素的細胞團塊,當這些能產生胰島素的球體細胞團塊移植到糖尿病小鼠,發現也能夠有效改善糖尿病小鼠的高血糖症狀。為了改善胰島來源的絕對缺乏以及移植後的胰島存活及功能不佳的兩項問題,本論文研究發現可透過維甲酸來增加胰島微血管,來改善移植胰島的存活與功能,更進一步可透過肝細胞重新編程產製具備胰島素分泌功能的細胞團塊,以改善胰島來源缺乏的問題。 | zh_TW |
dc.description.abstract | Diabetes mellitus is a metabolic disorder resulted from insulin deficiency or insulin resistance. The primary treatment for patients with type I diabetes (or insulin-dependent diabetes mellitus) that are absolutely deficient in insulin is insulin injection. However, insulin injection as a regimen for treating diabetes is unable to long-termly control blood sugar levels. Instead, islet transplantation is the potential way to sustainably modulate glycemic status. However, the shortage of donor islets and poor islet graft survival and function limit the potential use of islet transplantation to treat patients with type 1 diabetes. The major goal of the PhD thesis is trying to overcome the barrier of application of islet transplantation.
In the first part of the thesis, we analyzed and found that an essential micronutrient, vitamin A, is an important factor in embryogenesis. All-trans retinoic acid (atRA), the active metabolite of vitamin A, plays an essential role in regulating pancreatic development. We initially investigated how maternal vitamin A deficiency may affect fetal islet development and revealed that atRA is involved in regulating vascularized islet formation via modulating vascular endothelial growth factor secretion. Based on the observation, we next evaluated whether treatment with atRA can ameliorate diabetes. We found that administration of atRA could gradually decrease the blood glucose levels of diabetic mice, increase the amount of β-cells, and restore the vascular laminin expression. Furthermore, atRA induced the expression of vascular endothelial growth factor-A from the pancreatic islets, which mediated the restoration of islet vascularity and recovery of β-cell mass. Importantly, we showed atRA treatment significantly improved grafted islet functionality and vascularity and the combination of islet transplantation and atRA administration could rescue hyperglycemia in diabetic mice. The findings suggest vitamin A derivatives can potentially be used as a supplementary treatment to improve diabetes management and glycemic control. In the second part of the thesis, we tried to reprogram primary hepatocytes to Sox9-expressing progenitor cells in a three dimensional (3D) culture system. We found these Sox9-expressing progenitors could form spheroid on polyvinyl alcohol (PVA) substrates. In combination with overexpressing Pdx1, Ngn3 and MafA, these hepatocytes could further be reprogramed to insulin-producing clusters. Transplantation of insulin-producing clusters into diabetic mice was found to rescue hyperglycemia. In conclusion, these current works discovered that atRA treatment could improve survival and functionality of the grafted islets. Moreover, these works further developed a novel strategy to generate insulin-secreting cell clusters via hepatocyte reprogramming for transplantation. | en |
dc.description.provenance | Made available in DSpace on 2021-05-19T17:55:11Z (GMT). No. of bitstreams: 1 ntu-105-D96642003-1.pdf: 82030539 bytes, checksum: 4ec17accd4fa76d499c70ccc38b92a54 (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 致謝 I
摘要 II ABSTRACT IV CONTENTS VI LIST OF FIGURES IX LIST OF TABLES XII ABBREVIATION XIII CHAPTER 1. GENERAL INTRODUCTION 1 1.1. DIABETES MELLITUS AND TREATMENT OPTIONS 1 1.2. PANCREATIC ISLETS: ANATOMY AND FUNCTION 2 1.3. ISLET TRANSPLANTATION 4 1.4. THESIS OBJECTIVE 5 CHAPTER 2. ALL-TRANS RETINOIC ACID AMELIORATES GLYCEMIC CONTROL IN DIABETIC MICE VIA MODULATING PANCREATIC ISLET PRODUCTION OF VASCULAR ENDOTHELIAL GROWTH FACTOR-A 8 2.1. INTRODUCTION 9 2.1.1. Overview of retinoic acid (RA) metabolism 10 2.1.2. Vitamin A deficiency in diabetes 13 2.1.3. Vitamin A deficiency in islet development during embryogenesis 14 2.1.4. The vascular basement membrane in pancreatic islet 16 2.1.5. The role of VEGF in pancreatic islet 19 2.2. MATERIAL AND METHODS 21 2.2.1. Reagents 21 2.2.2. Animals, diets and experimental design 21 2.2.3. System for ex vivo culture of mouse embryonic pancreatic buds 22 2.2.4. Pancreatic islet isolation 23 2.2.5. Histology and immunohistochemistry 23 2.2.6. Immunofluorescence staining 24 2.2.7. Insulin and VEGF-A secretion assays 26 2.2.8. Measurement of insulin content 27 2.2.9. RNA preparation, RT-PCR and quantitative PCR analysis 27 2.2.10. Islet transplantation 27 2.2.11. Statistical analyses 28 2.3. RESULTS 29 2.3.1. Vitamin A deficiency impairs vascularization during endocrine pancreas development 29 2.3.2. Inhibition of endogenous retinoic acid biosynthesis reduced vascular laminin level and suppressed β-cell differentiation in embryonic pancreas 30 2.3.3. Retinoic acid receptor-mediated signaling enhances β-cell differentiation in embryonic pancreas 31 2.3.4. Retinoic acid regulates vascularization and β-cell differentiation via enhancing production of vascular endothelial growth factor-A 33 2.3.5. AtRA administration ameliorated the level of blood glucose of diabetic mice 35 2.3.6. AtRA enhances islet vascularization in diabetic mice 36 2.3.7. AtRA elevates vascular endothelial growth factor production in islets 37 2.3.8. AtRA improves islet graft vascularization and ameliorates hyperglycemia in diabetic mice 38 2.4. DISCUSSION 40 CHAPTER 3. REPROGRAMMING OF HEPATOCYTES INTO INSULIN-PRODUCING CELL CULTURES IN 3D SPHEROID CULTURES 44 3.1. INTRODUCTION 45 3.1.1. Potential role of reprogramming hepatocytes in pancreas regenerative medicine 46 3.1.2. Reprograming hepatocytes via 3D culture on Polyvinyl alcohol (PVA) conjugate membrane 48 3.1.3. Key factors regulating dedifferentiation of periportal hepatocyte 49 3.2. MATERIAL AND METHODS 52 3.2.1. FACS analysis and sorting. 52 3.2.2. FACS analysis and sorting. 53 3.2.3. Immunofluorescent staining. 53 3.2.3. EdU labeling of cultured hepatic spheres and EdU staining. 53 3.2.4. Ilumina mouse whole genome expression BeadChip 54 3.2.5. Mouse experiment 54 3.2.6. Statistical analyses 55 3.3. RESULTS 56 3.3.1. Reprogramming of periportal hepatocyte into Sox9-expressing progenitor cells 56 3.3.2. Characterization of Sox9-expressing progenitor cells derived from periportal hepatocyte reprogramming 58 3.3.3. Transplantation of sphere-type insulin-producing cells improves glycemic control 65 3.4. DISCUSSION 67 CHAPTER 4. FINAL DISCUSSION AND FUTURE PERSPECTIVES 73 REFERENCES 77 | |
dc.language.iso | en | |
dc.title | 利用維甲酸促進胰島微血管增生及透過肝細胞重新編程產製胰島素分泌細胞團塊來改善糖尿病的細胞治療 | zh_TW |
dc.title | Improving cell-replacement therapies for diabetes via enhancing islet vascularization with retinoic acid and generating insulin-producing cell clusters from hepatocyte reprogramming | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-1 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 沈家寧,宋麗英,何國牟,楊卿堯,吳耀銘 | |
dc.subject.keyword | 維甲酸,糖尿病,治療,胰島微血管增生,胰島素分泌細胞團塊, | zh_TW |
dc.subject.keyword | retinoic acid,diabetes,therapy,islet vascularization,insulin-producing cell clusters, | en |
dc.relation.page | 157 | |
dc.identifier.doi | 10.6342/NTU201603601 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2016-09-21 | |
dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
dc.contributor.author-dept | 生物科技研究所 | zh_TW |
Appears in Collections: | 生物科技研究所 |
Files in This Item:
File | Size | Format | |
---|---|---|---|
ntu-105-1.pdf | 80.11 MB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.