Pleiotropic roles of PDX-1 in the pancreas

Review of Diabetic Studies

Volumn 4, Issue 4, 2007, Pages 209-225

  Kaneto, Hideaki ^a   Miyatsuka, Takeshi ^a   Kawamori, Dan ^a   Matsuoka, Taka Aki ^a  

^a OSAKA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

Beta cell differentiation; Beta cell glucose toxicity; Diabetes; Pancreas development; PDX 1

Indexed keywords

ACETYLCYSTEINE; ALPHA TOCOPHEROL; ASCORBIC ACID; GLUCOKINASE; GLUCOSE TRANSPORTER 2; HYBRID PROTEIN; INSULIN; NEUROGENIC DIFFERENTIATION FACTOR; NEUROGENIN 3; PDX1 VP16 FUSION PROTEIN; PROBUCOL; TRANSCRIPTION FACTOR PDX 1; UNCLASSIFIED DRUG;

ANTIOXIDANT ACTIVITY; CELL ACTIVATION; CELL DIFFERENTIATION; CELL MATURATION; CELL PROTECTION; CYTOPATHOGENIC EFFECT; DIABETES MELLITUS; DRUG POTENTIATION; DRUG TARGETING; ENZYME ACTIVATION; GENE ACTIVATION; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE INACTIVATION; GENE INDUCTION; HUMAN; INSULIN RELEASE; INSULIN SYNTHESIS; MOLECULAR MECHANICS; NONHUMAN; ORGANOGENESIS; PANCREAS; PANCREAS ISLET BETA CELL; PANCREAS ISLET CELL; PLEIOTROPY; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN SYNTHESIS INHIBITION; REVIEW; TRANSCRIPTION INITIATION;

EID: 64549129278     PISSN: 16136071     EISSN: 16140575     Source Type: Journal    
DOI: 10.1900/RDS.2007.4.209     Document Type: Review

References (160)

1. Slack JM. Developmental biology of the pancreas. Development 1995. 121:1569-1580.
2. Edlund H. Transcribing pancreas. Diabetes 1998. 47:1817-1823. (Pubitemid 28549186)
3. Edlund H. Pancreatic organogenesis-developmental mechanisms and implications for therapy. Nat Rev Genet 2002. 3:524-532. (Pubitemid 34746877)
4. Murtaugh LC. Pancreas and beta-cell development: from the actual to the possible. Development 2007. 134:427-438. (Pubitemid 46332480)
5. Melloul D. Transcription factors in islet development and physiology: role of PDX-1 in beta-cell function. Ann N Y Acad Sci 2004. 1014:28-37. (Pubitemid 38594788)
6. Servitja JM, Ferrer J. Transcriptional networks controlling pancreatic development and beta cell function. Diabetologia 2004. 47:597-613. (Pubitemid 38658361)
7. Ohlsson H, Karlsson K, Edlund T. IPF1, a homeodomain-containing- transactivator of the insulin gene. EMBO J 1993. 12:4251-4259.
8. Miller CP, McGehee RE, Habener JF. IDX-1: a new homeodomain transcription factor expressed in rat pancreatic islets and duodenum that transactivates the somatostatin gene. EMBO J 1994. 13:1145-1156. (Pubitemid 24074721)
9. Leonard J, Peers B, Johnson T, Ferreri K, Lee S, Montminy MR. Characterization of somatostatin transactivating factor-1, a novel homeobox factor that stimulates somatostatin expression in pancreatic islet cells. Mol Endocrinol 1993. 7:1275-1283. (Pubitemid 23319110)
10. Jonsson J, Carlsson L, Edlund T, Edlund H. Insulin promoter-factor 1 is required for pancreas development in mice. Nature 1993. 37:606-609.
11. Guz Y, Montminy MR, Stein R, Leonard J, Gamer LW, Wright CV, Teitelmen G. Expression of murine STF-1, a putative insulin gene transcription factor, in beta cells of pancreas, duodenal epithelium and pancreatic exocrine and endocrine progenitors during ontogeny. Development 1995. 121:11-18.
12. Ahlgren U, Jonsson J, Edlund H. The morphogenesis of the pancreatic mesenchyme is uncoupled from that of the pancreatic epithelium in IPF1/PDX1-deficient mice. Development 1996. 122:1409-1416. (Pubitemid 26159631)
13. Offield MF, Jetton TL, Labosky P, Ray M, Stein RW, Magnuson MA, Hogan BL, Wright CV. PDX-1 is required for pancreas outgrowth and differentiation of the rostral duodenum. Development 1996. 122:983-985. (Pubitemid 26096002)
14. Kaneto H, Miyagawa J, KajimotoY, Yamamoto K, Watada H, Umayahara Y, Hanafusa Y, Matsuzawa Y, Yamasaki Y, Higashiyama S, Taniguchi N. Expression of heparin-binding epidermal growth factor-like growth factor during pancreas development: a potential role of PDX-1 in transcriptional activation. J Biol Chem 1997. 272:29137-29143. (Pubitemid 27498203)
15. Stoffers DA, Zinkin NT, Stanojevic V, Clarke WL, Habener JF. Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. Nat Genet 1997. 15:106-110. (Pubitemid 27014961)
16. Dutta S, Bonner-Weir S, Montminy M, Wright C. Regulatory factor linked to late-onset diabetes? Nature 1998. 392:560. (Pubitemid 28207703)
17. Stoffers DA, Heller RS, Miller CP, Habener JF. Developmental expression of the homeodomain protein IDX-1 in mice transgenic for an IDX-1 promoter/LacZ transcriptional reporter. Endocrinology 1999. 140:5374-5381. (Pubitemid 30687149)
18. Holland AM, Hale MA, Kagami H, Hammer RE, MacDonald RJ. Experimental control of pancreatic development and maintenance. Proc Natl Acad Sci USA 2002. 99:12236-12241.
19. Ferber S, Halkin A, Cohen H, Ber I, Einav Y, Goldberg I, Barshack I, Seijffers R, Kopolovic J, Kaiser N, Karasik A. Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia. Nat Med 2000. 6:568-572. (Pubitemid 30305908)
20. Heller RS, Stoffers DA, Bock T, Svenstrup K, Jensen J, Horn T, Miller CP, Habener JF, Madsen OD, Serup P. Improved glucose tolerance and acinar dysmorphogenesis by targeted expression of transcription factor PDX-1 to the exocrine pancreas. Diabetes 2001. 50:1553-1561. (Pubitemid 33639595)
21. Kojima H, Nakamura T, Fujita Y, Kishi A, Fujimiya M, Yamada S, Kudo M, Nishio Y, Maegawa H, Haneda M, Yasuda H, Kojima I, Seno M, Wong NC, Kikkawa R, Kashiwagi A. Combined expression of pancreatic duodenal homeobox 1 and islet factor 1 induces immature enterocytes to produce insulin. Diabetes 2002. 51:1398-1408. (Pubitemid 34826605)
22. Yoshida S, Kajimoto Y, Yasuda T, Watada H, Fujitani Y, Kosaka H, Gotow T, Miyatsuka T, Umayahara Y, Yamasaki Y, Hori M. PDX-1 induces differentiation of intestinal epithelioid IEC-6 into insulin-producing cells. Diabetes 2002. 51:2505-2513. (Pubitemid 34827400)
23. Noguchi H, Kaneto H, Weir GC, Bonner-Weir S. PDX-1 protein containing its own Antennapedia-like protein transduction domain can transduce pancreatic duct and islet cells. Diabetes 2003. 52:1732-1737. (Pubitemid 36792464)
24. Taniguchi H, Yamato E, Tashiro F, Ikegami H, Ogihara T, Miyazaki J. Beta-cell neogenesis induced by adenovirus-mediated gene delivery of transcription factor pdx-1 into mouse pancreas. Gene Ther 2003. 10:15-23. (Pubitemid 36175822)
25. Tang DQ, Cao LZ, Burkhardt BR, Xia CQ, Litherland SA, Atkinson MA, Yang LJ. In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow. Diabetes 2004. 53:1721-1732. (Pubitemid 38857030)
26. Miyatsuka T, Kaneto H, Kajimoto Y, Hirota S, Arakawa Y, Fujitani Y, Umayahara Y, Watada H, Yamasaki Y, Magnuson MA Miyazaki J, Hori M. Ectopically expressed PDX-1 in liver initiates endocrine and exocrine pancreas differentiation but causes dysmorphogenesis. Biochem Biophys Res Commun 2003. 310:1017-1025. (Pubitemid 37188724)
27. Kaneto H, Nakatani Y, Miyatsuka T, Matsuoka T, Matsuhisa M, Hori M, Yamasaki Y. PDX-1/VP16 fusion protein, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance. Diabetes 2005. 54:1009-1022. (Pubitemid 40446314)
28. Cao LZ, Tang DQ, Horb ME, Li SW, Yang LJ. High glucose is necessary for complete maturation of Pdx 1-VP16-expressing hepatic cells into functional insulin-producing cells. Diabetes 2004. 53:3168-3178. (Pubitemid 39564492)
29. Imai J, Katagiri H, Yamada T, Ishigaki Y, Ogihara T, Uno K, Hasegawa Y, Gao J, Ishihara H, Sasano H, Mizuguchi H, Asano T, Oka Y. Constitutively active PDX1 induced efficient insulin production in adult murine liver. Biochem Biophys Res Commun 2005. 326:402-409. (Pubitemid 39593561)
30. Petersen HV, Serup P, Leonard J, Michelsen BK, Madsen OD. Transcriptional regulation of the human insulin gene is dependent on the homeodomain protein STF1/IPF1 acting through the CT boxes. Proc Natl Acad Sci USA 1994. 91:10465-10469. (Pubitemid 24329018)
31. Peers B, Leonard J, Sharma S, Teitelman G, Montminy MR. Insulin expression in pancreatic islet cells relies on cooperative interactions between the helix loop helix factor E47 and the homeobox factor STF-1. Mol Endocrinol 1994. 8:1798-1806.
32. Waeber G, Thompson N, Nicod P, Bonny C. Transcriptional activation of the GLUT2 gene by the IPF-1/STF-1/IDX-1 homeobox factor. Mol Endocrinol 1996. 10:1327-1334. (Pubitemid 26423223)
33. Watada H, Kajimoto Y, Umayahara Y, Matsuoka T, Kaneto H, Fujitani Y, Kamada T, Kawamori R, Yamasaki Y. The human glucokinase gene beta-cell-type promoter: An essential role of insulin promoter factor 1 (IPF1)/PDX-1 in its activation in HIT-T15 cells. Diabetes 1996. 45:1478-1488. (Pubitemid 26357538)
34. Ahlgren U, Jonsson J, Jonsson L, Simu K, Edlund H. Beta-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the beta-cell phenotype and maturity onset diabetes. Genes Dev 1998. 12:1763-1768. (Pubitemid 28304328)
35. Wang H, Maechler P, Ritz-Laser B, Hagenfeldt KA, Ishihara H, Philippe J, Wollheim CB. Pdx1 level defines pancreatic gene expression pattern and cell lineage differentiation. J Biol Chem 2001. 276:25279-25286. (Pubitemid 37413012)
36. Brissova M, Shiota M., Nicholson WE, Gannon M, Knobel SM, Piston DW, Wright CV, Powers AC. Reduction in pancreatic transcription factor PDX-1 impairs glucose-stimulated insulin secretion. J Biol Chem 2002. 277:1125-11232. (Pubitemid 34952885)
37. Kulkarni RN, Jhala US, Winnay JN, Krajewski S, Montminy M, Kahn CR. PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistance. J Clin Invest 2004. 114:828-836. (Pubitemid 39578742)
38. Holland AM, Gonez LJ, Naselli G, MacDonald RJ, Harrison LC. Conditional expression demonstrates the role of the homeodomain transcription factor Pdx1 in maintenance and regeneration of beta-cells in the adult pancreas. Diabetes 2005. 54:2586-2595. (Pubitemid 41233579)
39. Herrera PL. Adult insulin- and glucagon-producing cells differentiate from two independent cell lineages. Development 2000. 127:2317-2322. (Pubitemid 30386571)
40. Gu G, Dubauskaite J, Melton DA. Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and distinct from duct progenitors. Development 2002. 129:2447-2457. (Pubitemid 34863851)
41. Kawaguchi Y, Cooper B, Gannon M, Ray M, MacDonald RJ, Wright CV. The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nat Genet 2002. 32:128-134. (Pubitemid 34977207)
42. Stoffers DA, Ferrer J, Clarke WL, Habener JF. Early-onset type-II diabetes mellitus (MODY4) linked to IPF1. Nat Genet 1997. 17(2):138-139.
43. Harrison KA, Thaler J, Pfaff SL, Gu H, Kehrl JH. Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9-deficient mice. Nat Genet 1999. 23:71-75. (Pubitemid 29418791)
44. Li H, Arber S, Jessell TM, Edlund H. Selective agenesis of the dorsal pancreas in mice lacking homeobox gene Hlxb9. Nat Genet 1999. 23:67-70. (Pubitemid 29418790)
45. Naya FJ, Stellrecht CM, Tsai MJ. Tissue-specific regulation of the insulin gene by a novel basic helix-loop-helix transcription factor. Genes Dev 1995. 9:1009-1019.
46. Naya FJ, Huang H, Qiu Y, Mutoh H, DeMayo F, Leiter AB, Tsai MJ. Diabetes, defective pancreatic morphogenesis, and abnormal enteroendocrine differentiation in BETA2/neuroD-deficient mice. Genes Dev 1997. 11:323-2334. (Pubitemid 27408530)
47. Kojima H, Fujimiya M, Matsumura K, Younan P, Imaeda H, Maeda M, Chan L. NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice. Nat Med 2003. 9:595-603. (Pubitemid 36597107)
48. Noguchi H, Bonner-Weir S, Wei FY, Matsushita M, Matsumoto S. BETA2/NeuroD protein can be transduced into cells due to an arginine- and lysine-rich sequence. Diabetes 2005. 54:2859-2866. (Pubitemid 41401080)
49. Sharma A, Stein R. Glucose-induced transcription of the insulin gene is mediated by factors required for beta-cell-type-specific expression. Mol Cell Biol 1994. 14:871-879. (Pubitemid 24036536)
50. German MS, Wang J. The insulin gene contains multiple transcriptional elements that respond to glucose. Mol Cell Biol 1994. 14:4067-4075. (Pubitemid 24160812)
51. Grapin-Botton A, Majithia AR, Melton DA. Key events of pancreas formation are triggered in gut endoderm by ectopic expression of pancreatic regulatory genes. Genes Dev 2001. 15:444-454. (Pubitemid 32187005)
52. Apelqvist A, Li H, Sommer L, Beatus P, Anderson DJ, Honjo T, de Angelis MH, Lendahl U, Edlund H. Notch signaling controls pancreatic cell differentiation. Nature 1999. 400:877-881. (Pubitemid 29406724)
53. Schwitzgebel VM, Scheel DW, Conners JR, Kalamaras J, Lee JE, Anderson DJ, Sussel L, Johnson JD, German MS. Expression of neurogenin3 reveals an islet cell precursor population in the pancreas. Development 2000. 127:3533-3542. (Pubitemid 30705974)
54. Gradwohl G, Dierich A, LeMeur M, Guillemot F. neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas. Proc Natl Acad Sci USA 2000. 97(4):1607-1611. (Pubitemid 30118489)
55. Watada, H. Neurogenin 3 is a key transcription factor for differentiation of the endocrine pancreas. Endocr J 2004. 51:255-264. (Pubitemid 38981064)
56. Dominguez-Bendala J, Klein D, Ribeiro M, Ricordi C, Inverardi L, Pastori R, Edlund H. TAT-mediated neurogenin 3 protein transduction stimulates pancreatic endocrine differentiation in vitro. Diabetes 2005. 54:720-726. (Pubitemid 40322074)
57. Huang HP, Liu M, Heithem M, El-Hodiri HM, Chu K, Jamrich M, Tsai MJ. Regulation of the pancreatic islet-specific gene BETA2 (neuroD) by neurogenin 3. Mol Cell Biol 2000. 20:3292-3307 (Pubitemid 30215041)
58. Watada H, Scheel DW, Leung J, German MS. Distinct gene expression programs function in progenitor and mature islet cells. J Biol Chem 2003. 278:17130-17140. (Pubitemid 36799591)
59. Smith SB, Gasa R, Watada H, Wang J, Griffen SC, German MS. Neurogenin3 and hepatic nuclear factor 1 cooperate in activating pancreatic expression of Pax4. J Biol Chem 2003. 278:38254-38259. (Pubitemid 37221715)
60. Watada H, Mirmira RG, Leung J, German MS. Transcriptional and translational regulation of beta-cell differentiation factor Nkx6.1. J Biol Chem 2000 275:34224-34230. (Pubitemid 30819187)
61. Jensen J, Pedersen EE, Galante P, Hald J, Heller RS, Ishibashi M, Kageyama R, Guillemot F, Serup P, Madsen OD. Control of endodermal endocrine development by Hes-1. Nat Genet 2000. 25:36-44. (Pubitemid 30041417)
62. Sumazaki R, Shiojiri N, Isoyama S, Masu M, Keino-Masu K, Osawa M, Nakauchi H, Kageyama R, Matsui A. Conversion of biliary system to pancreatic tissue in Hes1-deficient mice. Nat Genet 2004. 36:83-87. (Pubitemid 38056212)
63. Murtaugh LC, Stanger BZ, Kwan KM, Melton DA. Notch signaling controls multiple steps of pancreatic differentiation. Proc Natl Acad Sci USA 2003. 100:14920-14925. (Pubitemid 37517992)
64. Ahlgren U, Pfaff SL, Jessell TM, Edlund T, Edlund H. Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells. Nature 1997. 385:257-260. (Pubitemid 27043725)
65. Sosa-Pineda B, Chowdhury K, Torres M, Oliver G, Gruss P. The Pax4 gene is essential for differentiation of insulin-producing beta cells in the mammalian pancreas. Nature 1997. 386:399-402. (Pubitemid 27154480)
66. St-Onge L, Sosa-Pineda B, Chowdhury K, Mansouri A, Gruss P. Pax6 is required for differentiation of glucagon-producing alpha-cells in mouse pancreas. Nature 1997. 387(6631):406-409. (Pubitemid 27227205)
67. Sander M, Neubuser A, Kalamaras J, Ee HC, Martin GR, German MS. Genetic analysis reveals that PAX6 is required for normal transcription of pancreatic hormone genes and islet development. Genes Dev 1997. 11:1662-1673. (Pubitemid 27300592)
68. Sander M, Sussel L, Conners J, Scheel D, Kalamaras J, Dela Cruz F, Schwitzgebel V, Hayes-Jordan A, German M. Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of beta-cell formation in the pancreas. Development 2000. 127:5533-5540. (Pubitemid 32049205)
69. Sussel L, Kalamaras J, Hartigan-O'Connor DJ, Meneses JJ, Pedersen RA, Rubenstein JL, German MS. Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to arrested differentiation of pancreatic beta cells. Development 1998. 125:2213-2221. (Pubitemid 28336383)
70. Fujitani Y, Kajimoto Y, Yasuda T, Matsuoka T, Kaneto H, Umayahara Y, Fujita N, Watada H, Miyazaki J, Yamasaki Y, Hori M. Identification of a portable repression domain and an E1A-responsive activation domain in Pax 4: a possible role of Pax 4 as a transcriptional repressor in the pancreas. Mol Cell Biol 1999. 19:8281-8291. (Pubitemid 30414022)
71. Smith SB, Ee HC, Conners JR, German MS. Paired-homeodomain transcription factor PAX4 acts as a transcriptional repressor in early pancreatic development. Mol Cell Biol 1999. 19:8272-8280. (Pubitemid 30414021)
72. Prado CL, Pugh-Bernard AE, Elghazi L, Sosa-Pineda B, Sussel L. Ghrelin cells replace insulin-producing beta cells in two mouse models of pancreas development. Proc Natl Acad Sci USA 2004. 101:2924-2929. (Pubitemid 38327712)
73. Heller RS, Jenny M, Collombat P, Mansouri A, Tomasetto C, Madsen OD, Mellitzer G, Gradwohl G, Serup P. Genetic determinants of pancreatic epsilon-cell development. Dev Biol 2005. 286(1):217-224. (Pubitemid 41394059)
74. Pedersen JK, Nelson SB, Jorgensen MC, Henseleit KD, Fujitani Y, Wright CV, Sander M, Serup P. Endodermal expression of Nkx6 genes depends differentially on Pdx1. Dev Biol 2005. 288:487-501. (Pubitemid 41790757)
75. Collombat P, Mansouri A, Hecksher-Sorensen J, Serup P, Krull J, Gradwohl G, Gruss P. Opposing actions of Arx and Pax4 in endocrine pancreas development. Genes Dev 2003. 17:2591-2603. (Pubitemid 37271428)
76. Matsuoka T, Zhao L, Artner I, Jarrett HW, Friedman D, Means A, Stein R. Members of the large Maf transcription family regulate insulin gene transcription in islet beta cells. Mol Cell Biol 2003. 23:6049-6062. (Pubitemid 37013085)
77. Olbrot M, Rud J, Moss LG, Sharma A. Identification of beta-cell-specific insulin gene transcription factor RIPE3b1 as mammalian MafA. Proc Natl Acad Sci USA 2002. 99:6737-6742. (Pubitemid 34526201)
78. Kataoka K, Han SI, Shioda S, Hirai M, Nishizawa M, Handa H. MafA is a glucose-regulated and pancreatic beta-cell-specific transcriptional activator for the insulin gene. J Biol Chem 2002. 277:49903-49910. (Pubitemid 36014439)
79. Zhang C, Moriguchi T, Kajihara M, Esaki R, Harada A, Shimohata H, Oishi H, Hamada M, Morito N, Hasegawa K, Kudo T, Engel JD, Yamamoto M, Takahashi S. MafA is a key regulator of glucose-stimulated insulin secretion. Mol Cell Biol 2005. 25:4969-4976. (Pubitemid 40781098)
80. Kaneto H, Matsuoka T, Nakatani Y, Miyatsuka T, Matsuhisa M, Hori M, Yamasaki Y. A crucial role of MafA as a novel therapeutic target for diabetes. J Biol Chem 2005. 280:15047-15052. (Pubitemid 40562858)
81. Matsuoka T, Kaneto H, Stein R, Miyatsuka T, Kawamori D, Henderson E, Kojima I, Matsuhisa M, Hori M, Yamasaki Y. MafA regulates expression of genes important to islet beta cell function. Mol Endocrinol 2007. 21:2764-2774. (Pubitemid 350035157)
82. Lumelsky N, Blondel O, Laeng P, Velasco I, Ravin R, McKay R. Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 2001. 292:1389-1394. (Pubitemid 32476228)
83. Soria B, Roche E, Berna G, Leon-Quinto T, Reig JA, Martin F. Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes 2000. 49:157-162. (Pubitemid 30070992)
84. Assady S, Maor G, Amit M, Itskovitz-Eldor J, Skorecki K, Tzukerman M. Insulin production by human embryonic stem cells. Diabetes 2001. 50:1691-1697. (Pubitemid 33641584)
85. Moritoh Y, Yamato E, Yasui Y, Miyazaki S, Miyazaki J. Analysis of insulin-producing cells during in vitro differentiation from feeder-free embryonic stem cells. Diabetes 2003. 52:1163-1168. (Pubitemid 36523351)
86. Hori Y, Rulifson IC, Tsai BC, Heit JJ, Cahoy JD, Kim SK. Growth inhibitors promote differentiation of insulin-producing tissue from embryonic stem cells. Proc Natl Acad Sci USA 2002. 99:16105-16110. (Pubitemid 35462756)
87. Bonner-Weir S, Taneja M, Weir GC, Tatarkiewicz K, Song KH, Sharma A, O'Neil JJ. In vitro cultivation of human islets expanded ductal tissue. Proc Natl Acad Sci USA 2000. 97:7999-8004. (Pubitemid 30460762)
88. Taniguchi H, Yamato E, Tashiro F, Ikegami H, Ogihara T, Miyazaki J. Beta-cell neogenesis induced by adenovirus-mediated gene delivery of transcription factor pdx-1 into mouse pancreas. Gene Ther 2003. 10:15-23. (Pubitemid 36175822)
89. Ramiya VK, Maraist M, Arfors KE, Schatz DA, Peck AB, Cornelius JG. Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nat Med 2000. 6:278-282. (Pubitemid 30148619)
90. Zulewsky H, Abraham EJ, Gerlach MJ, Daniel PB, Moritz W, Muller B, Vallejo M, Thomas MK, Habener JF. Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes 2001. 50:521-533. (Pubitemid 32195216)
91. Seaberg RM, Smukler SR, Kieffer TJ, Enikolopov G, Asghar Z, Wheeler MB, Korbutt G, van der Kooy D. Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat Biotechnol 2004. 22:1115-1124. (Pubitemid 39166849)
92. Yang L, Li S, Hatch H, Ahrens K, Cornelius JG, Petersen BE, Peck AB. In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells. Proc Natl Acad Sci USA 2002. 99:8078-8083. (Pubitemid 34651008)
93. Yamada S, Yamamoto Y, Nagasawa M, Hara A, Kodera T, Kojima I. In vitro transdifferentiation of mature hepatocytes into insulin-producing cells. Endocr J 2006. 53:789-795 (Pubitemid 46045125)
94. Ianus A, Holz GG, Theise ND, Hussain MA. In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest 2003. 111:843-850. (Pubitemid 37074959)
95. Suzuki A, Nakauchi H, Taniguchi H. Prospective isolation of multipotent pancreatic progenitors using flow-cytometric cell sorting. Diabetes 2004. 53:2143-2152. (Pubitemid 38970768)
96. Horb ME, Shen CN, Tosh D, Slack JM. Experimental conversion of liver to pancreas. Curr Biol 2003. 13(2):105-115. (Pubitemid 36154337)
97. Noguchi H, Matsushita M, Matsumoto S, Lu YF, Matsui H, Bonner-Weir S. Mechanism of PDX-1 protein transduction. Biochem Biophys Res Commun 2005. 332:68-74. (Pubitemid 40719458)
98. Wu H, Macfarlane WM, Tadayyon M, Arch JR, James RF, Docherty K. Insulin stimulates pancreatic-duodenal homoeobox factor-1 (PDX1) DNA-binding activity and insulin promoter activity in pancreatic beta cells. Biochem J 1999. 344:813-818. (Pubitemid 30032529)
99. Macfarlane WM, Shepherd RM, Cosgrove KE, James RF, Dunne MJ, Docherty K. Glucose modulation of insulin mRNA levels is dependent on transcription factor PDX-1 and occurs independently of changes in intracellular Ca2+. Diabetes 2000. 49(3):418-423. (Pubitemid 30131787)
100. Elrick LJ, Docherty K. Phosphorylation-dependent nucleocytoplasmic shuttling of pancreatic duodenal homeobox-1. Diabetes 2001. 50:2244-2252. (Pubitemid 33641908)
101. McKinnon CM, Docherty K. Pancreatic duodenal homeobox-1, PDX-1, a major regulator of beta cell identity and function. Diabetologia 2001. 44:1203-1214. (Pubitemid 33010496)
102. Reimer MK, Ahren B. Altered beta-cell distribution of pdx-1 and GLUT-2 after a short-term challenge with a high-fat diet in C57BL/6J mice. Diabetes 2002. 51:S138-S143. (Pubitemid 34761509)
103. Bell GI, Polonsky KS. Diabetes mellitus and genetically programmed defects in beta-cell function. Nature 2001. 414:788-791. (Pubitemid 34000781)
104. Gannon M, Gamer LW, Wright CV. Regulatory regions driving developmental and tissue-specific expression of the essential pancreatic gene pdx1. Dev Biol 2001. 238(1):185-201. (Pubitemid 32939295)
105. Gerrish K, Gannon M, Shih D, Henderson E, Stoffel M, Wright CV, Stein R. Pancreatic beta cell-specific transcription of the pdx-1 gene. The role of conserved upstream control regions and their hepatic nuclear factor 3beta sites. J Biol Chem 2000. 275:3485-3492. (Pubitemid 30083057)
106. Shih DQ, Heimesaat M, Kuwajima S, Stein R, Wright CV, Stoffel M. Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta. Proc Natl Acad Sci USA 2002. 99:3818-3823. (Pubitemid 34252189)
107. Marshak S, Benshushan E, Shoshkes M, Havin L, Cerasi E, Melloul D. Functional conservation of regulatory elements in the pdx-1 gene: PDX-1 and hepatocyte nuclear factor 3beta transcription factors mediate beta-cell-specific expression. Mol Cell Biol 2000. 20(20):7583-7590. (Pubitemid 30736882)
108. Gerrish K, Cissell MA, Stein R. The role of hepatic nuclear factor 1alpha and PDX-1 in transcriptional regulation of the pdx-1 gene. J Biol Chem 2001. 276:47775-47784. (Pubitemid 37370670)
109. Ben-Shushan E, Marshak S, Shoshkes M, Cerasi E, Melloul D. A pancreatic beta-cell-specific enhancer in the human PDX-1 gene is regulated by hepatocyte nuclear factor 3beta (HNF-3beta), HNF-1alpha, and SPs transcription factors. J Biol Chem 2001. 276:17533-17540. (Pubitemid 37411570)
110. Samaras SE, Cissell MA, Gerrish K, Wright CV, Gannon M, Stein R. Conserved sequences in a tissue-specific regulatory region of the pdx-1 gene mediate transcription in pancreatic beta cells: Role for hepatocyte nuclear factor 3beta and Pax6. Mol Cell Biol 2002. 22:4702-4713. (Pubitemid 34620406)
111. Samaras SE, Zhao L, Means A, Henderson E, Matsuoka TA, Stein R. The islet beta cell-enriched RIPE3b1/Maf transcription factor regulates pdx-1 expression. J Biol Chem 2003. 278:12263-12270. (Pubitemid 36800208)
112. Jacquemin P, Lemaigre FP, Rousseau GG. The Onecut transcription factor HNF-6 (OC-1) is required for timely specification of the pancreas and acts upstream of Pdx-1 in the specification cascade. Dev Biol 2003. 258:105-116. (Pubitemid 36627659)
113. Wu KL, Gannon M, Peshavaria M, Offield MF, Henderson E, Ray M, Marks A, Gamer LW, Wright CV, Stein R. Hepatocyte nuclear factor 3beta is involved in pancreatic beta-cell-specific transcription of the pdx-1 gene. Mol Cell Biol 1997. 17:6002-6013. (Pubitemid 27411108)
114. Miyatsuka T, Matsuoka T, Shiraiwa T, Yamamoto T, Kojima I, Kaneto H. Ptf1a and RBP-J cooperate in activating Pdx1 gene expression through binding to Area III. Biochem Biophys Res Commun 2007. 362:905-909. (Pubitemid 47390659)
115. Obata J, Yano M, Mimura H, Goto T, Nakayama R, Mibu Y, Oka C, Kawaichi M. p48 subunit of mouse PTF1 binds to RBP-Jkappa/CBF-1, the intracellular mediator of Notch signalling, and is expressed in the neural tube of early stage embryos. Genes Cells 2001. 6(4):345-360. (Pubitemid 32401280)
116. Beres TM, Masui T, Swift GH, Shi L, Henke RM, MacDonald RJ. PTF1 is an organ-specific and Notch-independent basic helix-loop-helix complex containing the mammalian Suppressor of Hairless (RBP-J) or its paralogue, RBP-L. Mol Cell Biol 2006. 26:117-130.
117. Krapp A, Knofler M, Ledermann B, Burki K, Berney C, Zoerkler N, Hagenbuchle O, Wellauer PK. The bHLH protein PTF1-p48 is essential for the formation of the exocrine and the correct spatial organization of the endocrine pancreas. Genes Dev 1998. 12:3752-3763. (Pubitemid 29019655)
118. Fujikura J, Hosoda K, Iwakura H, Tomita T, Noguchi M, Masuzaki H, Tanigaki K, Yabe D, Honjo T, Nakao K. Notch/Rbp-j signaling prevents premature endocrine and ductal cell differentiation in the pancreas. Cell Metab 2006. 3:59-65.
119. Sellick GS, Barker KT, Stolte-Dijkstra I, Fleischmann C, Coleman RJ, Garrett C, Gloyn AL, Edghill EL, Hattersleyv AT, Wellauer PK, Goodwin G, Houlston RS. Mutations in PTF1A cause pancreatic and cerebellar agenesis. Nat Genet 2004. 36:1301-1305. (Pubitemid 39577939)
120. Mashima H, Yamada S, Tajima T, Seno M, Yamada H, Takeda J, Kojima I. Genes expressed during the differentiation of pancreatic AR42J cells into insulin-secreting cells. Diabetes 1999. 48:304-309. (Pubitemid 29061103)
121. Kitamura R, Ogata T, Tanaka Y, Motoyoshi K, Seno M, Takei I, Umezawa K, Kojima I. Conophylline and betacellulin-delta4: an effective combination of differentiation factors for pancreatic beta cells. Endocr J 2007. 54:255-264. (Pubitemid 46798648)
122. Wiebe PO, Kormish JD, Roper VT, Fujitani Y, Alston NI, Zaret KS, Wright CV, Stein RW, Gannon M. Ptf1a binds to and activates area III, a highly conserved region of the Pdx1 promoter that mediates early pancreas-wide Pdx1 expression. Mol Cell Biol 2007. 27(11):4093-4104. (Pubitemid 47011006)
123. Fujitani Y, Fujitani S, Boyer DF, Gannon M, Kawaguchi Y, Ray M, Shiota M, Stein RW, Magnuson MA, Wright CV. Targeted deletion of a cis-regulatory region reveals differential gene dosage requirements for Pdx1 in foregut organ differentiation and pancreas formation. Genes Dev 2006. 20:253-266. (Pubitemid 43112942)
124. Song SY, Gannon M, Washington MK, Scoggins CR, Meszoely IM, Goldenring JR, Marino CR, Sandgren EP, Coffey RJ Jr, Wright CV, Leach SD. Expansion of Pdx1-expressing pancreatic epithelium and islet neogenesis in transgenic mice overexpressing transforming growth factor alpha. Gastroenterology 1999. 117:1416-1426.
125. Koizumi M, Doi R, Toyoda E, Masui T, Tulachan SS, Kawaguchi Y, Fujimoto K, Gittes GK, Imamura M. Increased PDX-1 expression is associated with outcome in patients with pancreatic cancer. Surgery 2003. 134:260-266. (Pubitemid 37070347)
126. Jensen JN, Cameron E, Garay MV, Starkey TW, Gianani R, Jensen J. Recapitulation of elements of embryonic development in adult mouse pancreatic regeneration. Gastroenterology 2005. 128:728-741. (Pubitemid 40585375)
127. Miyatsuka T, Kaneto H, Shiraiwa T, Matsuoka T, Yamamoto K, Kato K, Nakamura Y, Akira S, Takeda K, Kajimoto Y, Yamasaki Y, Sandgren EP, Kawaguchi Y, Wright CV, Fujitani Y. Persistent expression of PDX-1 causes acinar-to-ductal transition through Stat3 activation. Genes Dev 2006. 20(11):1435-1440. (Pubitemid 43830650)
128. Soria B, Roche E, Berna G, Leon-Quinto T, Reig JA, Martin F. Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes 2000. 49:157-162. (Pubitemid 30070992)
129. Sharma A, Olson LK, Robertson RP, Stein R. The reduction of insulin gene transcription in HIT-T15 beta cells chronically exposed to high glucose concentration is associated with the loss of RIPE3b1 and STF-1 transcription factor expression. Mol Endocrinol 1995. 9:1127-1134.
130. Olson LK, Redmon JB, Towle HC, Robertson RP. Chronic exposure of HIT cells to high glucose concentrations paradoxically decreases insulin gene transcription and alters binding of insulin gene regulatory protein. J Clin Invest 1993. 92:514-519. (Pubitemid 23209037)
131. Poitout V, Olson LK, Robertson RP. Chronic exposure of betaTC-6 cells to supraphysiologic concentrations of glucose decreases binding of the RIPE3b1 insulin gene transcription activator. J Clin Invest 1996. 97:1041-1046. (Pubitemid 26070584)
132. Jonas JC, Sharma A, Hasenkamp W, Iikova H, Patane G, Laybutt R, Bonner-Weir S, Weir GC. Chronic hyperglycemia triggers loss of pancreatic beta cell differentiation in an animal model of diabetes. J Biol Chem 1999. 274:14112-14121. (Pubitemid 129518719)
133. Robertson RP, Zhang HJ, Pyzdrowski KL, Walseth TF. Preservation of insulin mRNA levels and insulin secretion in HIT cells by avoidance of chronic exposure to high glucose concentrations. J Clin Invest 1992. 90:320-325.
134. Dandona P, Thusu K, Cook S, Snyder B, Makowski J, Armstrong D, Nicotera T. Oxidative damage to DNA in diabetes mellitus. Lancet 1996, 347:444-445. (Pubitemid 26054071)
135. Baynes JW, Thorpe SR. Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 1999. 48:1-9. (Pubitemid 29019345)
136. Ihara Y, Toyokuni S, Uchida K, Odaka H, Tanaka T, Ikeda H, Hiai H, Seino Y, Yamada Y. Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats, a model of type 2 diabetes. Diabetes 1999. 48:927-932. (Pubitemid 29153099)
137. Matsuoka T, Kajimoto Y, Watada H, Kaneto H, Kishimoto M, Umayahara Y, Fujitani Y, Kamada T, Kawamori R, Yamasaki Y. Glycation-dependent, reactive oxygen species-mediated suppression of the insulin gene promoter activity in HIT cells. J Clin Invest 1997. 99:144-150. (Pubitemid 27058305)
138. Kaneto H, Kajimoto Y, Miyagawa J, Matsuoka T, Fujitani Y, Umayahara Y, Hanafusa T, Matsuzawa Y, Yamasaki Y, Hori M. Beneficial effects of antioxidants for diabetes: possible protection of pancreatic beta-cells against glucose toxicity. Diabetes 1999. 48:2398-2406. (Pubitemid 30395432)
139. Tanaka Y, Gleason CE, Tran PO, Harmon JS, Robertson RP. Prevention of glucose toxicity in HIT-T15 cells and Zucker diabetic fatty rats by antioxidants. Proc Natl Acad Sci USA 1999. 96(19):10857-10862. (Pubitemid 29442234)
140. Kajimoto Y, Matsuoka T, Kaneto H, Watada H, Fujitani Y, Kishimoto M, Sakamoto K, Matsuhisa M, Kawamori R, Yamasaki Y, Hori M. Induction of glycation suppresses glucokinase gene expression in HIT-T15 cells. Diabetologia 1999. 42:417-1424. (Pubitemid 30012313)
141. Kaneto H, Xu G, Song KH, Suzuma K, Bonner-Weir S, Sharma A, Weir GC. Activation of the hexosamine pathway leads to deterioration of pancreatic beta-cell function by provoking oxidative stress. J Biol Chem 2001. 276:31099-31104. (Pubitemid 37384975)
142. Tanaka Y, Tran POT, Harmon J, Robertson RP. A role of glutathione peroxidase in protecting pancreatic beta cells against oxidative stress in a model of glucose toxicity. Proc Natl Acad Sci USA 2002. 99:12363-12368.
143. Gorogawa S, Kajimoto Y, Umayahara Y, Kaneto H, Watada H, Kuroda A, Kawamori D, Yasuda T, Matsuhisa M, Yamasaki Y, Hori M. Probucol preserves pancreatic beta-cell function through reduction of oxidative stress in type 2 diabetes. Diabetes Res Clin Prac 2002. 57:1-10. (Pubitemid 34463014)
144. Robertson RP, Harmon J, Tran PO, Tanaka Y, Takahashi H. Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes 2003. 52:581-587. (Pubitemid 36323562)
145. Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction? Diabetes 2003. 52:1-8. (Pubitemid 36042100)
146. Unger RH. Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology 2003. 144(12):5159-5165. (Pubitemid 37476041)
147. Poitout V, Robertson RP. Minireview: secondary beta-cell failure in type 2 diabetes - a convergence of glucotoxicity and lipotoxicity. Endocrinology 2002. 143(2):339-342. (Pubitemid 34107184)
148. Moore PC, Ugas MA, Hagman DK, Parazzoli SD, Poitout V. Evidence against the involvement of oxidative stress in fatty acid inhibition of insulin secretion. Diabetes 2004. 53:2610-2616. (Pubitemid 39299269)
149. Hagman DK, Hays LB, Parazzoli SD, Poitout V. Palmitate inhibits insulin gene expression by altering PDX-1 nuclear localization and reducing MafA expression in isolated rat islets of Langerhans. J Biol Chem 2005. 280:32413-32418. (Pubitemid 41361852)
150. Sakai K, Matsumoto K, Nishikawa T, Suefuji M, Nakamura K, Hirashima Y, Kawashima J, Shirotani T, Ichinose K, Brownlee M, Araki E. Mitochondrial reactive oxygen species reduce insulin secretion by pancreatic beta-cells. Biochem Biophys Res Commun 2003. 300:216-222. (Pubitemid 36042955)
151. Robertson RP. Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes. J Biol Chem 2004. 271:42351-42354.
152. Kaneto H, Nakatani Y, Kawamori D, Miyatsuka T, Matsuoka T. Involvement of oxidative stress and the JNK pathway in glucose toxicity. Rev Diabet Stud 2004. 1(4):165-174.
153. Harmon JS, Stein R, Robertson RP. Oxidative stress-mediated, post-translational loss of MafA protein as a contributing mechanism to loss of insulin gene expression in glucotoxic beta cells. J Biol Chem 2005. 280:11107-11113. (Pubitemid 40418415)
154. Lenzen S, Drinkgern J, Tiedge M. Low antioxidant enzyme gene expression in pancreatic islets compared with various other mouse tissues. Free Rad Biol Med 1996. 20:463-466. (Pubitemid 26077870)
155. Tiedge M, Lortz S, Drinkgern J, Lenzen S. Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. Diabetes 1997. 46:1733-1742. (Pubitemid 27456404)
156. Kaneto H, Xu G, Fujii N, Kim S, Bonner-Weir S, Weir GC. Involvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression of insulin gene expression. J Biol Chem 2002. 277:30010-30018.
157. Kawamori D, Kajimoto Y, Kaneto H, Umayahara Y, Fujitani Y, Miyatsuka T, Watada H, Leibiger IB, Yamasaki Y, Hori M. Oxidative stress induces nucleo-cytoplasmic translocation of pancreatic transcription factor PDX-1 through activation of c-Jun N-terminal kinase. Diabetes 2003. 52:2896-2904. (Pubitemid 37466858)
158. Kitamura T, Nakae J, Kitamura Y, Kido Y, Biggs WH 3rd, Wright CV, White MF, Arden KC, Accili D. The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. J Clin Invest 2002. 110:1839-1847.
159. Nakae J, Biggs WH 3rd, Kitamura T, Cavenee WK, Wright CV, Arden KC, Accili D. Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. Nat Genet 2002. 32(2):245-253.
160. Kawamori D, Kaneto H, Nakatani Y, Matsuoka T, Matsuhisa M, Hori M, Yamasaki Y. The forkhead transcription factor Foxo1 bridges the JNK pathway and the transcription factor PDX-1 through its intracellular translocation. J Biol Chem 2006. 281:1091-1098.