PDX-1 functions as a master factor in the pancreas

Frontiers in Bioscience

Volumn 13, Issue 16, 2008, Pages 6406-6420

  Kaneto, Hideaki ^a   Matsuoka, Taka Aki ^a   Miyatsuka, Takeshi ^a   Kawamori, Dan ^a   Katakami, Naoto ^a   Yamasaki, Yoshimitsu ^a   Matsuhisa, Munehide ^a  

^a OSAKA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

Beta Cell; Differentiation; Dysfunction; Glucose; JNK; MafA; Oxidative Stress; Pancreas; Pathway; PDX 1; Review; Toxicity; Transcription Factor

Indexed keywords

DNA BINDING PROTEIN; HOMEODOMAIN PROTEIN; INSULIN; INSULIN PROMOTER FACTOR 1; MAFA PROTEIN, HUMAN; TRANSACTIVATOR PROTEIN; TRANSCRIPTION FACTOR MAF;

ANIMAL; ANIMAL MODEL; CELL DIFFERENTIATION; CYTOLOGY; ENHANCER REGION; GENETICS; GROWTH, DEVELOPMENT AND AGING; HUMAN; HYPERGLYCEMIA; METABOLISM; METAPLASIA; MOUSE; PANCREAS; PANCREAS ISLET BETA CELL; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; REVIEW; SECRETION;

ANIMALS; CELL DIFFERENTIATION; DNA-BINDING PROTEINS; ENHANCER ELEMENTS (GENETICS); HOMEODOMAIN PROTEINS; HUMANS; HYPERGLYCEMIA; INSULIN; INSULIN-SECRETING CELLS; MAF TRANSCRIPTION FACTORS, LARGE; METAPLASIA; MICE; MODELS, ANIMAL; PANCREAS; TRANS-ACTIVATORS;

EID: 52049119853     PISSN: 27686701     EISSN: 27686698     Source Type: Journal    
DOI: None     Document Type: Article

References (131)

1. G. C. Weir, D. R. Laybutt, H. Kaneto, S. Bonner-Weir & A. Sharma: Beta-cell adaptation and decompensation during the progression of diabetes. Diabetes 50 Suppl 1, S154-159 (2001) (Pubitemid 32148243)
2. V. Poitout & R. P. Robertson: Minireview: Secondary beta-cell failure in type 2 diabetes-a convergence of glucotoxicity and lipotoxicity. Endocrinology 143, 339-342 (2002) (Pubitemid 34107184)
3. H. Ohlsson, K. Karlsson & T. Edlund: IPF1, a homeodomain-containing transactivator of the insulin gene. Embo J 12, 4251-4259 (1993) (Pubitemid 23302039)
4. C. P. Miller, R. E. McGehee, Jr. & J. F. Habener: IDX-1: a new homeodomain transcription factor expressed in rat pancreatic islets and duodenum that transactivates the somatostatin gene. Embo J 13, 1145-1156 (1994) (Pubitemid 24074721)
5. J. Leonard, B. Peers, T. Johnson, K. Ferreri, S. Lee & M. R. Montminy: Characterization of somatostatin transactivating factor-1, a novel homeobox factor that stimulates somatostatin expression in pancreatic islet cells. Mol Endocrinol 7, 1275-1283 (1993) (Pubitemid 23319110)
6. J. Jonsson, L. Carlsson, T. Edlund & H. Edlund: Insulin-promoter- factor 1 is required for pancreas development in mice. Nature 371, 606-609 (1994) (Pubitemid 24315741)
7. Y. Guz, M. R. Montminy, R. Stein, J. Leonard, L. W. Gamer, C. V. Wright & G. Teitelman: 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 121, 11-18 (1995)
8. U. Ahlgren, J. Jonsson & H. Edlund: The morphogenesis of the pancreatic mesenchyme is uncoupled from that of the pancreatic epithelium in IPF1/PDX1-deficient mice. Development 122, 1409-1416 (1996) (Pubitemid 26159631)
9. M. F. Offield, T. L. Jetton, P. A. Labosky, M. Ray, R. W. Stein, M. A. Magnuson, B. L. Hogan & C. V. Wright: PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. Development 122, 983-995 (1996) (Pubitemid 26096002)
10. H. Kaneto, J. Miyagawa, Y. Kajimoto, K. Yamamoto, H. Watada, Y. Umayahara, T. Hanafusa, Y. Matsuzawa, Y. Yamasaki, S. Higashiyama & N. Taniguchi: 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 272, 29137-29143 (1997) (Pubitemid 27498203)
11. D. A. Stoffers, N. T. Zinkin, V. Stanojevic, W. L. Clarke & J. F. Habener: Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. Nat Genet 15, 106-110 (1997) (Pubitemid 27014961)
12. S. Dutta, S. Bonner-Weir, M. Montminy & C. Wright: Regulatory factor linked to late-onset diabetes? Nature 392, 560 (1998) (Pubitemid 28207703)
13. D. A. Stoffers, R. S. Heller, C. P. Miller & J. F. Habener: Developmental expression of the homeodomain protein IDX-1 in mice transgenic for an IDX-1 promoter/lacZ transcriptional reporter. Endocrinology 140, 5374-5381 (1999)
14. A. M. Holland, M. A. Hale, H. Kagami, R. E. Hammer & R. J. MacDonald: Experimental control of pancreatic development and maintenance. Proc Natl Acad Sci U S A 99, 12236-12241 (2002)
15. D. Melloul: Transcription factors in islet development and physiology: role of PDX-1 in beta-cell function. Ann N Y Acad Sci 1014, 28-37 (2004) (Pubitemid 38594788)
16. K. A. Harrison, J. Thaler, S. L. Pfaff, H. Gu & J. H. Kehrl: Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9-deficient mice. Nat Genet 23, 71-75 (1999) (Pubitemid 29418791)
17. H. Li, S. Arber, T. M. Jessell & H. Edlund: Selective agenesis of the dorsal pancreas in mice lacking homeobox gene Hlxb9. Nat Genet 23, 67-70 (1999) (Pubitemid 29418790)
18. U. Ahlgren, S. L. Pfaff, T. M. Jessell, T. Edlund & H. Edlund: Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells. Nature 385, 257-260 (1997) (Pubitemid 27043725)
19. B. Sosa-Pineda, K. Chowdhury, M. Torres, G. Oliver & P. Gruss: The Pax4 gene is essential for differentiation of insulin-producing beta cells in the mammalian pancreas. Nature 386, 399-402 (1997) (Pubitemid 27154480)
20. L. St-Onge, B. Sosa-Pineda, K. Chowdhury, A. Mansouri & P. Gruss: Pax6 is required for differentiation of glucagon-producing alpha-cells in mouse pancreas. Nature 387, 406-409 (1997) (Pubitemid 27227205)
21. M. Sander, A. Neubuser, J. Kalamaras, H. C. Ee, G. R. Martin & M. S. German: Genetic analysis reveals that PAX6 is required for normal transcription of pancreatic hormone genes and islet development. Genes Dev 11, 1662-1673 (1997) (Pubitemid 27300592)
22. M. Sander, L. Sussel, J. Conners, D. Scheel, J. Kalamaras, F. Dela Cruz, V. Schwitzgebel, A. Hayes-Jordan & M. German: Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of beta-cell formation in the pancreas. Development 127, 5533-5540 (2000) (Pubitemid 32049205)
23. L. Sussel, J. Kalamaras, D. J. Hartigan-O'Connor, J. J. Meneses, R. A. Pedersen, J. L. Rubenstein & M. S. German: Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to arrested differentiation of pancreatic beta cells. Development 125, 2213-2221 (1998) (Pubitemid 28336383)
24. Y. Fujitani, Y. Kajimoto, T. Yasuda, T. A. Matsuoka, H. Kaneto, Y. Umayahara, N. Fujita, H. Watada, J. I. Miyazaki, Y. Yamasaki & M. Hori: Identification of a portable repression domain and an E1A-responsive activation domain in Pax4: a possible role of Pax4 as a transcriptional repressor in the pancreas. Mol Cell Biol 19, 8281-8291 (1999) (Pubitemid 30414022)
25. S. B. Smith, H. C. Ee, J. R. Conners & M. S. German: Paired-homeodomain transcription factor PAX4 acts as a transcriptional repressor in early pancreatic development. Mol Cell Biol 19, 8272-8280 (1999) (Pubitemid 30414021)
26. C. L. Prado, A. E. Pugh-Bernard, L. Elghazi, B. Sosa-Pineda & L. Sussel: Ghrelin cells replace insulin-producing beta cells in two mouse models of pancreas development. Proc Natl Acad Sci U S A 101, 2924-2929 (2004) (Pubitemid 38327712)
27. R. S. Heller, M. Jenny, P. Collombat, A. Mansouri, C. Tomasetto, O. D. Madsen, G. Mellitzer, G. Gradwohl & P. Serup: Genetic determinants of pancreatic epsilon-cell development. Dev Biol 286, 217-224 (2005) (Pubitemid 41394059)
28. J. K. Pedersen, S. B. Nelson, M. C. Jorgensen, K. D. Henseleit, Y. Fujitani, C. V. Wright, M. Sander & P. Serup: Endodermal expression of Nkx6 genes depends differentially on Pdx1. Dev Biol 288, 487-501 (2005) (Pubitemid 41790757)
29. P. Jacquemin, H. Yoshitomi, Y. Kashima, G. G. Rousseau, F. P. Lemaigre & K. S. Zaret: An endothelial-mesenchymal relay pathway regulates early phases of pancr eas development.Dev Bio l 290, 189-199 (2006) (Pubitemid 43083614)
30. S. Ferber, A. Halkin, H. Cohen, I. Ber, Y. Einav, I. Goldberg, I. Barshack, R. Seijffers, J. Kopolovic, N. Kaiser & A. Karasik: Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia. Nat Med 6, 568-572 (2000) (Pubitemid 30305908)
31. R. S. Heller, D. A. Stoffers, T. Bock, K. Svenstrup, J. Jensen, T. Horn, C. P. Miller, J. F. Habener, O. D. Madsen & P. Serup: Improved glucose tolerance and acinar dysmorphogenesis by targeted expression of transcription factor PDX-1 to the exocrine pancreas. Diabetes 50, 1553-1561 (2001) (Pubitemid 33639595)
32. H. Kojima, T. Nakamura, Y. Fujita, A. Kishi, M. Fujimiya, S. Yamada, M. Kudo, Y. Nishio, H. Maegawa, M. Haneda, H. Yasuda, I. Kojima, M. Seno, N. C. Wong, R. Kikkawa & A. Kashiwagi: Combined expression of pancreatic duodenal homeobox 1 and islet factor 1 induces immature enterocytes to produce insulin. Diabetes 51, 1398-1408 (2002) (Pubitemid 34826605)
33. S. Yoshida, Y. Kajimoto, T. Yasuda, H. Watada, Y. Fujitani, H. Kosaka, T. Gotow, T. Miyatsuka, Y. Umayahara, Y. Yamasaki & M. Hori: PDX-1 induces differentiation of intestinal epithelioid IEC-6 into insulin-producing cells. Diabetes 51, 2505-2513 (2002) (Pubitemid 34827400)
34. H. Noguchi, H. Kaneto, G. C. Weir & S. Bonner-Weir: PDX-1 protein containing its own antennapedia-like protein transduction domain can transduce pancreatic duct and islet cells. Diabetes 52, 1732-1737 (2003) (Pubitemid 36792464)
35. H. Taniguchi, E. Yamato, F. Tashiro, H. Ikegami, T. Ogihara & J. Miyazaki: beta-cell neogenesis induced by adenovirus-mediated gene delivery of transcription factor pdx-1 into mouse pancreas. Gene Ther 10, 15-23 (2003) (Pubitemid 36175822)
36. D. Q. Tang, L. Z. Cao, B. R. Burkhardt, C. Q. Xia, S. A. Litherland, M. A. Atkinson & L. J. Yang: In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow. Diabetes 53, 1721-1732 (2004) (Pubitemid 38857030)
37. T. Miyatsuka, H. Kaneto, Y. Kajimoto, S. Hirota, Y. Arakawa, Y. Fujitani, Y. Umayahara, H. Watada, Y. Yamasaki, M. A. Magnuson, J. Miyazaki & M. Hori: Ectopically expressed PDX-1 in liver initiates endocrine and exocrine pancreas differentiation but causes dysmorphogenesis. Biochem Biophys Res Commun 310, 1017-1025 (2003) (Pubitemid 37188724)
38. H. Kaneto, Y. Nakatani, T. Miyatsuka, T. A. Matsuoka, M. Matsuhisa, M. Hori & Y. Yamasaki: PDX-1/VP16 fusion protein, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance. Diabetes 54, 1009-1022 (2005) (Pubitemid 40446314)
39. L. Z. Cao, D. Q. Tang, M. E. Horb, S. W. Li & L. J. Yang: High glucose is necessary for complete maturation of Pdx1-VP16-expressing hepatic cells into functional insulin-producing cells. Diabetes 53, 3168-3178 (2004) (Pubitemid 39564492)
40. J. Imai, H. Katagiri, T. Yamada, Y. Ishigaki, T. Ogihara, K. Uno, Y. Hasegawa, J. Gao, H. Ishihara, H. Sasano, H. Mizuguchi, T. Asano & Y. Oka: Constitutively active PDX1 induced efficient insulin production in adult murine liver. Biochem Biophys Res Commun 326, 402-409 (2005) (Pubitemid 39593561)
41. H. V. Petersen, P. Serup, J. Leonard, B. K. Michelsen & O. D. Madsen: Transcriptional regulation of the human insulin gene is dependent on the homeodomain protein STF1/IPF1 acting through the CT boxes. Proc Natl Acad Sci U S A 91, 10465-10469 (1994) (Pubitemid 24329018)
42. B. Peers, J. Leonard, S. Sharma, G. Teitelman & M. R. Montminy: 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 8, 1798-1806 (1994)
43. G. Waeber, N. Thompson, P. Nicod & C. Bonny: Transcriptional activation of the GLUT2 gene by the IPF-1/STF-1/IDX-1 homeobox factor. Mol Endocrinol 10, 1327-1334 (1996) (Pubitemid 26423223)
44. H. Watada, Y. Kajimoto, Y. Umayahara, T. Matsuoka, H. Kaneto, Y. Fujitani, T. Kamada, R. Kawamori & Y. Yamasaki: The human glucokinase gene beta-cell-type promoter: an essential role of insulin promoter factor 1/PDX-1 in its activation in HIT-T15 cells. Diabetes 45, 1478-1488 (1996) (Pubitemid 26357538)
45. U. Ahlgren, J. Jonsson, L. Jonsson, K. Simu & H. Edlund: beta-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the beta-cell phenotype and maturity onset diabetes. Genes Dev 12, 1763-1768 (1998) (Pubitemid 28304328)
46. H. Wang, P. Maechler, B. Ritz-Laser, K. A. Hagenfeldt, H. Ishihara, J. Philippe & C. B. Wollheim: Pdx1 level defines pancreatic gene expression pattern and cell lineage differentiation. J Biol Chem 276, 25279-25286 (2001)
47. M. Brissova, M. Shiota, W. E. Nicholson, M. Gannon, S. M. Knobel, D. W. Piston, C. V. Wright & A. C. Powers: Reduction in pancreatic transcription factor PDX-1 impairs glucose-stimulated insulin secretion. J Biol Chem 277, 11225-11232 (2002) (Pubitemid 34952885)
48. S. K. Chakrabarti, J. C. James & R. G. Mirmira: Quantitative assessment of gene targeting in vitro and in vivo by the pancreatic transcription factor, Pdx1. Importance of chromatin structure in directing promoter binding. J Biol Chem 277, 13286-13293 (2002) (Pubitemid 34952700)
49. R. N. Kulkarni, U. S. Jhala, J. N. Winnay, S. Krajewski, M. Montminy & C. R. Kahn: PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that ccurs in response to insulin resistance. J Clin Invest 114, 828-836 (2004) (Pubitemid 39578742)
50. A. M. Holland, L. J. Gonez, G. Naselli, R. J. Macdonald & L. C. Harrison: Conditional expression demonstrates the role of the homeodomain transcription factor Pdx1 in maintenance and regeneration of beta-cells in the adult pancreas. Diabetes 54, 2586-2595 (2005) (Pubitemid 41233579)
51. D. A. Stoffers, J. Ferrer, W. L. Clarke & J. F. Habener: Early-onset type-II diabetes mellitus (MODY4) linked to IPF1. Nat Genet 17, 138-139 (1997)
52. F. J. Naya, C. M. Stellrecht & M. J. Tsai: Tissue-specific regulation of the insulin gene by a novel basic helix-loop-helix transcription factor. Genes Dev 9, 1009-1019 (1995)
53. F. J. Naya, H. P. Huang, Y. Qiu, H. Mutoh, F. J. DeMayo, A. B. Leiter & M. J. Tsai: Diabetes, defective pancreatic morphogenesis, and abnormal enteroendocrine differentiation in BETA2/neuroD-deficient mice. Genes Dev 11, 2323-2334 (1997) (Pubitemid 27408530)
54. H. Kojima, M. Fujimiya, K. Matsumura, P. Younan, H. Imaeda, M. Maeda & L. Chan: NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and everses diabetes in mice. Nat Med 9, 596-603 (2003) (Pubitemid 36597107)
55. H. Noguchi, S. Bonner-Weir, F. Y. Wei, M. Matsushita & S. Matsumoto: BETA2/NeuroD protein can be transduced into cells due to an arginine- and lysine-rich sequence. Diabetes 54, 2859-2866 (2005) (Pubitemid 41401080)
56. M. T. Malecki, U. S. Jhala, A. Antonellis, L. Fields, A. Doria, T. Orban, M. Saad, J. H. Warram, M. Montminy & A. S. Krolewski: Mutations in NEUROD1 are ssociated with the development of type 2 diabetes mellitus. Nat Genet 23, 323-328 (1999) (Pubitemid 29526431)
57. A. Sharma & R. Stein: Glucose-induced transcription of the insulin gene is mediated by factors required for beta-cell-type-specific expression. Mol Cell Biol 14, 871-879 (1994) (Pubitemid 24036536)
58. M. S. German & J. Wang: The insulin gene contains multiple transcriptional elements that respond to glucose. Mol Cell Biol 14, 4067-4075 (1994) (Pubitemid 24160812)
59. A. Grapin-Botton, A. R. Majithia & D. A. Melton: Key events of pancreas formation are triggered in gut endoderm by ectopic expression of pancreatic regulatory genes. Genes Dev 15, 444-454 (2001) (Pubitemid 32187005)
60. A. Apelqvist, H. Li, L. Sommer, P. Beatus, D. J. Anderson, T. Honjo, M. Hrabe de Angelis, U. Lendahl & H. Edlund: Notch signalling controls pancreatic cell differentiation. Nature 400, 877-881 (1999) (Pubitemid 29406724)
61. V. M. Schwitzgebel, D. W. Scheel, J. R. Conners, J. Kalamaras, J. E. Lee, D. J. Anderson, L. Sussel, J. D. Johnson & M. S. German: Expression of neurogenin3 reveals an islet cell precursor population in the pancreas. Development 127, 3533-3542 (2000)
62. G. Gradwohl, A. Dierich, M. LeMeur & F. Guillemot: neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas. Proc Natl Acad Sci U S A 97, 1607-1611 (2000) (Pubitemid 30118489)
63. G. Gu, J. Dubauskaite & D. A. Melton: Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development 129, 2447-2457 (2002) (Pubitemid 34863851)
64. Y. Heremans, M. Van De Casteele, P. in't Veld, G. Gradwohl, P. Serup, O. Madsen, D. Pipeleers & H. Heimberg: Recapitulation of embryonic neuroendocrine differentiation in adult human pancreatic duct cells expressing neurogenin 3. J Cell Biol 159, 303-312 (2002)
65. J. Dominguez-Bendala, D. Klein, M. Ribeiro, C. Ricordi, L. Inverardi, R. Pastori & H. Edlund: TAT-mediated neurogenin 3 protein transduction stimulates pancreatic endocrine differentiation in vitro. Diabetes 54, 720-726 (2005) (Pubitemid 40322074)
66. G. I. Bell & K. S. Polonsky: Diabetes mellitus and genetically programmed defects in beta-cell function. Nature 414, 788-791 (2001) (Pubitemid 34000781)
67. D. Q. Shih, M. Heimesaat, S. Kuwajima, R. Stein, C. V. Wright & M. Stoffel: 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 U S A 99, 3818-3823 (2002) (Pubitemid 34252189)
68. J. M. Servitja & J. Ferrer: Transcriptional networks controlling pancreatic development and beta cell function. Diabetologia 47, 597-613 (2004) (Pubitemid 38658361)
69. K. Gerrish, M. Gannon, D. Shih, E. Henderson, M. Stoffel, C. V. Wright & R. Stein: 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 275, 3485-3492 (2000) (Pubitemid 30083057)
70. S. Marshak, E. Benshushan, M. Shoshkes, L. Havin, E. Cerasi & D. Melloul: 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 20, 7583-7590 (2000)
71. K. Gerrish, M. A. Cissell & R. Stein: The role of hepatic nuclear factor 1 alpha and PDX-1 in transcriptional regulation of the pdx-1 gene. J Biol Chem 276, 47775-7784 (2001)
72. E. Ben-Shushan, S. Marshak, M. Shoshkes, E. Cerasi & D. Melloul: 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 276, 17533-17540 (2001)
73. S. E. Samaras, M. A. Cissell, K. Gerrish, C. V. Wright, M. Gannon & R. Stein: Conserved sequences in a tissue-specific regulatory region of the pdx-1 gene mediate transcription in Pancreatic beta cells: role for hepatocyte nuclear factor 3 beta and Pax6. Mol Cell Biol 22, 4702-4713 (2002) (Pubitemid 34620406)
74. S. E. Samaras, L. Zhao, A. Means, E. Henderson, T. A. Matsuoka & R. Stein: The islet beta cell-enriched RIPE3b1/Maf transcription factor regulates pdx-1 expression. J Biol Chem 278, 12263-12270 (2003) (Pubitemid 36800208)
75. P. Jacquemin, F. P. Lemaigre & G. G. Rousseau: 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 258, 105-116 (2003) (Pubitemid 36627659)
76. K. L. Wu, M. Gannon, M. Peshavaria, M. F. Offield, E. Henderson, M. Ray, A. Marks, L. W. Gamer, C. V. Wright & R. Stein: Hepatocyte nuclear factor 3beta is involved in pancreatic beta-cell-specific transcription of the pdx-1 gene. Mol Cell Biol 17, 6002-6013 (1997) (Pubitemid 27411108)
77. M. Gannon, L. W. Gamer & C. V. Wright: Regulatory regions driving developmental and tissue-specific expression of the essential pancreatic gene pdx1. Dev Biol 238, 185-201 (2001) (Pubitemid 32939295)
78. Y. Fujitani, S. Fujitani, D. F. Boyer, M. Gannon, Y. Kawaguchi, M. Ray, M. Shiota, R. W. Stein, M. A. Magnuson & C. V. Wright: Targeted deletion of a cis-regulatory region reveals differential gene dosage requirements for Pdx1 in foregut organ differentiation and pancreas formation. Genes Dev 20, 253-266 (2006) (Pubitemid 43112942)
79. S. Y. Song, M. Gannon, M. K. Washington, C. R. Scoggins, I. M. Meszoely, J. R. Goldenring, C. R. Marino, E. P. Sandgren, R. J. Coffey, Jr., C. V. Wright & S. D. Leach: Expansion of Pdx1-expressing pancreatic epithelium and islet neogenesis in transgenic mice overexpressing transforming growth factor alpha. Gastroenterology 117, 1416-1426 (1999)
80. M. Koizumi, R. Doi, E. Toyoda, T. Masui, S. S. Tulachan, Y. Kawaguchi, K. Fujimoto, G. K. Gittes & M. Imamura: Increased PDX-1 expression is associated with outcome in patients with pancreatic cancer. Surgery 134, 260-266 (2003) (Pubitemid 37070347)
81. J. N. Jensen, E. Cameron, M. V. Garay, T. W. Starkey, R. Gianani & J. Jensen: Recapitulation of elements of embryonic development in adult mouse pancreatic regeneration. Gastroenterology 128, 728-741 (2005) (Pubitemid 40585375)
82. T. Miyatsuka, H. Kaneto, T. Shiraiwa, T. A. Matsuoka, K. Yamamoto, K. Kato, Y. Nakamura, S. Akira, K. Takeda, Y. Kajimoto, Y. Yamasaki, E. P. Sandgren, Y. Kawaguchi, C. V. Wright & Y. Fujitani: Persistent expression of PDX-1 in the pancreas causes acinar-to-ductal metaplasia through Stat3 activation. Genes Dev 20, 1435-1440 (2006) (Pubitemid 43830650)
83. Y. Kawaguchi, B. Cooper, M. Gannon, M. Ray, R. J. MacDonald & C. V. Wright: The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nat Genet 32, 128-134 (2002) (Pubitemid 34977207)
84. B. Soria, E. Roche, G. Berna, T. Leon-Quinto, J. A. Reig & F. Martin: Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes 49, 157-162 (2000) (Pubitemid 30070992)
85. S. Assady, G. Maor, M. Amit, J. Itskovitz-Eldor, K. L. Skorecki & M. Tzukerman: Insulin production by human embryonic stem cells. Diabetes 50, 1691-1697 (2001) (Pubitemid 33641584)
86. Y. Moritoh, E. Yamato, Y. Yasui, S. Miyazaki & J. Miyazaki: Analysis of insulin-producing cells during in vitro differentiation from feeder-free embryonic stem cells. Diabetes 52, 1163-1168 (2003) (Pubitemid 36523351)
87. Y. Hori, I. C. Rulifson, B. C. Tsai, J. J. Heit, J. D. Cahoy & S. K. Kim: Growth inhibitors promote differentiation of insulin-producing tissue from embryonic stem cells. Proc Natl Acad Sci U S A 99, 16105-16110 (2002) (Pubitemid 35462756)
88. S. Bonner-Weir, M. Taneja, G. C. Weir, K. Tatarkiewicz, K. H. Song, A. Sharma & J. J. O'Neil: In vitro cultivation of human islets from expanded ductal tissue. Proc Natl Acad Sci U S A 97, 7999-8004 (2000) (Pubitemid 30460762)
89. V. K. Ramiya, M. Maraist, K. E. Arfors, D. A. Schatz, A. B. Peck & J. G. Cornelius: Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nat Med 6, 278-282 (2000) (Pubitemid 30148619)
90. H. Zulewski, E. J. Abraham, M. J. Gerlach, P. B. Daniel, W. Moritz, B. Muller, M. Vallejo, M. K. Thomas & J. F. Habener: Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes 50, 521-533 (2001) (Pubitemid 32195216)
91. R. M. Seaberg, S. R. Smukler, T. J. Kieffer, G. Enikolopov, Z. Asghar, M. B. Wheeler, G. Korbutt & D. van der Kooy: Clonal identification of multipotent recursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat Biotechnol 22, 1115-1124 (2004) (Pubitemid 39166849)
92. L. Yang, S. Li, H. Hatch, K. Ahrens, J. G. Cornelius, B. E. Petersen & A. B. Peck: In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells. Proc Natl Acad Sci U S A 99, 8078-8083 (2002) (Pubitemid 34651008)
93. M. Zalzman, S. Gupta, R. K. Giri, I. Berkovich, B. S. Sappal, O. Karnieli, M. A. Zern, N. Fleischer & S. Efrat: Reversal of hyperglycemia in mice by using human expandable insulin-producing cells differentiated from fetal liver progenitor cells. Proc Natl Acad Sci U S A 100, 7253-7258 (2003) (Pubitemid 36706425)
94. A. Ianus, G. G. Holz, N. D. Theise & M. A. Hussain: In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest 111, 843-850 (2003) (Pubitemid 37074959)
95. A. Suzuki, H. Nakauchi & H. Taniguchi: Prospective isolation of multipotent pancreatic progenitors using flow-cytometric cell sorting. Diabetes 53, 2143-2152 (2004) (Pubitemid 38970768)
96. M. E. Horb, C. N. Shen, D. Tosh & J. M. Slack: Experimental conversion of liver to pancreas. Curr Biol 13, 105-115 (2003) (Pubitemid 36154337)
97. A. Sharma, L. K. Olson, R. P. Robertson & R. Stein: 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 9, 1127-1134 (1995)
98. L. K. Olson, J. B. Redmon, H. C. Towle & R. P. Robertson: 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 92, 514-519 (1993) (Pubitemid 23209037)
99. M. Olbrot, J. Rud, L. G. Moss & A. Sharma: Identification of beta-cell-specific insulin gene transcription factor RIPE3b1 as mammalian MafA. Proc Natl Acad Sci U S A 99, 6737-6742 (2002) (Pubitemid 34526201)
100. K. Kataoka, S. I. Han, S. Shioda, M. Hirai, M. Nishizawa & H. Handa: MafA is a glucose-regulated and pancreatic beta-cell-specific transcriptional activator for the insulin gene. J Biol Chem 277, 49903-49910 (2002) (Pubitemid 36014439)
101. T. A. Matsuoka, L. Zhao, I. Artner, H. W. Jarrett, D. Friedman, A. Means & R. Stein: Members of the large Maf transcription family regulate insulin gene transcription in islet beta cells. Mol Cell Biol 23, 6049-6062 (2003) (Pubitemid 37013085)
102. T. A. Matsuoka, I. Artner, E. Henderson, A. Means, M. Sander & R. Stein: The MafA transcription factor appears to be responsible for tissue-specific expression of insulin. Proc Natl Acad Sci U S A 101, 2930-2933 (2004) (Pubitemid 38327713)
103. H. Kaneto, T. A. Matsuoka, Y. Nakatani, T. Miyatsuka, M. Matsuhisa, M. Hori & Y. Yamasaki: A crucial role of MafA as a novel therapeutic target for diabetes. J Biol Chem 280, 15047-15052 (2005) (Pubitemid 40562858)
104. C. Zhang, T. Moriguchi, M. Kajihara, R. Esaki, A. Harada, H. Shimohata, H. Oishi, M. Hamada, N. Morito, K. Hasegawa, T. Kudo, J. D. Engel, M. Yamamoto & S. Takahashi: MafA is a key regulator of glucose-stimulated insulin secretion. Mol Cell Biol 25, 4969-4976 (2005) (Pubitemid 40781098)
105. V. Poitout, L. K. Olson & R. P. Robertson: Chronic exposure of betaTC-6 cells to supraphysiologic concentrations of glucose decreases binding of the RIPE3b1 insulin gene transcription activator. J Clin Invest 97, 1041-1046 (1996) (Pubitemid 26070584)
106. J. C. Jonas, A. Sharma, W. Hasenkamp, H. Ilkova, G. Patane, R. Laybutt, S. Bonner-Weir & G. C. Weir: Chronic hyperglycemia triggers loss of pancreatic beta cell differentiation in an animal model of diabetes. J Biol Chem 274, 14112-14121 (1999)
107. R. P. Robertson, H. J. Zhang, K. L. Pyzdrowski & T. F. Walseth: Preservation of insulin mRNA levels and insulin secretion in HIT cells by avoidance of chronic exposure to high glucose concentrations. J Clin Invest 90, 320-325 (1992)
108. P. Dandona, K. Thusu, S. Cook, B. Snyder, J. Makowski, D. Armstrong & T. Nicotera: Oxidative damage to DNA in diabetes mellitus. Lancet 347, 444-445 (1996) (Pubitemid 26054071)
109. J. W. Baynes & S. R. Thorpe: Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 48, 1-9 (1999) (Pubitemid 29019345)
110. Y. Ihara, S. Toyokuni, K. Uchida, H. Odaka, T. Tanaka, H. Ikeda, H. Hiai, Y. Seino & Y. Yamada: Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats, a model of type 2 diabetes. Diabetes 48, 927-932 (1999) (Pubitemid 29153099)
111. T. Matsuoka, Y. Kajimoto, H. Watada, H. Kaneto, M. Kishimoto, Y. Umayahara, Y. Fujitani, T. Kamada, R. Kawamori & Y. Yamasaki: Glycation-dependent, reactive oxygen species-mediated suppression of the insulin gene promoter activity in HIT cells. J Clin Invest 99, 144-150 (1997) (Pubitemid 27058305)
112. H. Kaneto, Y. Kajimoto, J. Miyagawa, T. Matsuoka, Y. Fujitani, Y. Umayahara, T. Hanafusa, Y. Matsuzawa, Y. Yamasaki & M. Hori: Beneficial effects of antioxidants in diabetes: possible protection of pancreatic beta-cells against glucose toxicity. Diabetes 48, 2398-2406 (1999) (Pubitemid 30395432)
113. Y. Tanaka, C. E. Gleason, P. O. Tran, J. S. Harmon & R. P. Robertson: Prevention of glucose toxicity in HIT-T15 cells and Zucker diabetic fatty rats by antioxidants. Proc Natl Acad Sci U S A 96, 10857-10862 (1999) (Pubitemid 29442234)
114. Y. Kajimoto, T. Matsuoka, H. Kaneto, H. Watada, Y. Fujitani, M. Kishimoto, K. Sakamoto, M. Matsuhisa, R. Kawamori, Y. Yamasaki & M. Hori: Induction of glycation suppresses glucokinase gene expression in HIT-T15 cells. Diabetologia 42, 1417-1424 (1999) (Pubitemid 30012313)
115. H. Kaneto, G. Xu, K. H. Song, K. Suzuma, S. Bonner-Weir, A. Sharma & G. C. Weir: Activation of the hexosamine pathway leads to deterioration of pancreatic beta-cell function through the induction of oxidative stress. J Biol Chem 276, 31099-31104 (2001)
116. Y. Tanaka, P. O. Tran, J. Harmon & R. P. Robertson: A role for glutathione peroxidase in protecting pancreatic beta cells against oxidative stress in a model of glucose toxicity. Proc Natl Acad Sci U S A 99, 12363-12368 (2002)
117. S. Gorogawa, Y. Kajimoto, Y. Umayahara, H. Kaneto, H. Watada, A. Kuroda, D. Kawamori, T. Yasuda, M. Matsuhisa, Y. Yamasaki & M. Hori: Probucol preserves pancreatic beta-cell function through reduction of oxidative stress in type 2 diabetes. Diabetes Res Clin Pract 57, 1-10 (2002) (Pubitemid 34463014)
118. R. P. Robertson, J. Harmon, P. O. Tran, Y. Tanaka & H. Takahashi: Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes 52, 581-587 (2003) (Pubitemid 36323562)
119. J. L. Evans, I. D. Goldfine, B. A. Maddux & G. M. Grodsky: Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction? Diabetes 52, 1-8 (2003) (Pubitemid 36042100)
120. R. H. Unger: Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology 144, 5159-5165 (2003) (Pubitemid 37476041)
121. P. C. Moore, M. A. Ugas, D. K. Hagman, S. D. Parazzoli & V. Poitout: Evidence against the involvement of oxidative stress in fatty acid inhibition of insulin secretion. Diabetes 53, 2610-2616 (2004) (Pubitemid 39299269)
122. D. K. Hagman, L. B. Hays, S. D. Parazzoli & V. Poitout: Palmitate inhibits insulin gene expression by altering PDX-1 nuclear localization and reducing MafA expression in isolated rat islets of Langerhans. J Biol Chem 280, 32413-32418 (2005) (Pubitemid 41361852)
123. K. Sakai, K. Matsumoto, T. Nishikawa, M. Suefuji, K. Nakamaru, Y. Hirashima, J. Kawashima, T. Shirotani, K. Ichinose, M. Brownlee & E. Araki: Mitochondrial reactive oxygen species reduce insulin secretion by pancreatic beta-cells. Biochem Biophys Res Commun 300, 216-222 (2003) (Pubitemid 36042955)
124. R. P. Robertson: Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes. J Biol Chem 279, 42351-42354 (2004)
125. H. Kaneto, T. A. Matsuoka, Y. Nakatani, D. Kawamori, T. Miyatsuka, M. Matsuhisa & Y. Yamasaki: Oxidative stress, ER stress, and the JNK pathway in type 2 diabetes. J Mol Med 83, 429-439 (2005) (Pubitemid 40922165)
126. J. S. Harmon, R. Stein & R. P. Robertson: 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 280, 11107-11113 (2005) (Pubitemid 40418415)
127. S. Lenzen, J. Drinkgern & M. Tiedge: Low antioxidant enzyme gene expression in pancreatic islets compared with various other mouse tissues. Free Radic Biol Med 20, 463-466 (1996) (Pubitemid 26077870)
128. M. Tiedge, S. Lortz, J. Drinkgern & S. Lenzen: Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. Diabetes 46, 1733-1742 (1997) (Pubitemid 27456404)
129. H. Kaneto, G. Xu, N. Fujii, S. Kim, S. Bonner-Weir & G. C. Weir: Involvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression of insulin gene expression. J Biol Chem 277, 30010-30018 (2002)
130. D. Kawamori, Y. Kajimoto, H. Kaneto, Y. Umayahara, Y. Fujitani, T. Miyatsuka, H. Watada, I. B. Leibiger, Y. Yamasaki & M. Hori: Oxidative stress induces nucleo-cytoplasmic translocation of pancreatic transcription factor PDX-1 through activation of c-Jun NH (2)-terminal kinase. Diabetes 52, 2896-2904 (2003) (Pubitemid 37466858)
131. D. Kawamori, H. Kaneto, Y. Nakatani, T. A. Matsuoka, M. Matsuhisa, M. Hori & Y. Yamasaki: The forkhead transcription factor Foxo1 bridges the JNK pathway and the transcription factor PDX-1 through its intracellular translocation. J Biol Chem 281, 1091-1098 (2006)