192
Views
13
CrossRef citations to date
0
Altmetric
Review

Transcription factors as therapeutic targets for diabetes

, &
Pages 1431-1442 | Published online: 14 Oct 2008

Bibliography

  • Slack JM. Developmental biology of the pancreas. Development 1995;121:1569-80
  • Edlund H. Pancreatic organogenesis-developmental mechanisms and implications for therapy. Nat Rev Genet 2002;3:524-32
  • Zaret KS. Genetic programming of liver and pancreas progenitors: lessons for stem-cell differentiation. Nat Rev Genet 2008;9:329-40
  • Oliver-Krasinski JM, Stoffers DA. On the origin of the β cell. Genes Dev 2008;22:1998-2021
  • A Kim SK, Hebrok M, Melton DA. Notochord to endoderm signaling is required for pancreas development. Development 1997;124:4243-52
  • Hebrok M, Kim SK, Melton DA. Notochord repression of endodermal Sonic hedgehog permits pancreas development. Genes Dev 1998;12:1705-13
  • Lammert E, Cleaver O, Melton D. Induction of pancreatic differentiation by signals from blood vessels. Science 2001;294:564-7
  • Yoshitomi H, Zaret KS. Endothelial cell interactions initiate dorsal pancreas development by selectively inducing the transcription factor Ptf1a. Development 2004;131:807-17
  • Jacquemin P, Yoshitomi H, Kashima Y, et al. An endothelial-mesenchymal relay pathway regulates early phases of pancreas development. Dev Biol 2006;290:189-99
  • Jonsson J, Carlsson L, Edlund T, Edlund H. Insulin-promoter-factor 1 is required for pancreas development in mice. Nature 1994;371:606-9
  • Offield MF, Jetton TL, Labosky PA, et al. PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. Development 1996;122:983-95
  • 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;122:1409-16
  • Fujitani Y, Fujitani S, Boyer DF, et al. Targeted deletion of a cis-regulatory region reveals differential gene dosage requirements for Pdx1 in foregut organ differentiation and pancreas formation. Genes Dev 2006;20:253-66
  • Kaneto H, Miyagawa J, Kajimoto Y, et al. 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;272:29137-43
  • Ahlgren U, Jonsson J, Jonsson L, et al. β-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the β-cell phenotype and maturity onset diabetes. Genes Dev 1998;12:1763-8
  • Dutta S, Bonner-Weir S, Montminy M, Wright C. Regulatory factor linked to late-onset diabetes? Nature 1998;392:560
  • Kaneto H, Kajimoto Y, Miyagawa J, et al. Beneficial effects of antioxidants in diabetes: possible protection of pancreatic β-cells against glucose toxicity. Diabetes 1999;48:2398-406
  • Johnson JD, Ahmed NT, Luciani DS, et al. Increased islet apoptosis in Pdx1+/- mice. J Clin Invest 2003;111:1147-60
  • Kulkarni RN, Jhala US, Winnay JN, et al. PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistance. J Clin Invest 2004;114:828-36
  • Heimberg H, Bouwens L, Heremans Y, et al. Adult human pancreatic duct and islet cells exhibit similarities in expression and differences in phosphorylation and complex formation of the homeodomain protein Ipf-1. Diabetes 2000;49:571-9
  • Gu G, Dubauskaite J, Melton DA. Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development 2002;129:2447-57
  • Stoffers DA, Zinkin NT, Stanojevic V, et al. Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. Nat Genet 1997;15:106-10
  • 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;10:1327-34
  • Watada H, Kajimoto Y, Umayahara Y, et al. 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 1996;45:1478-88
  • Watada H, Kajimoto Y, Kaneto H, et al. Involvement of the homeodomain-containing transcription factor PDX-1 in islet amyloid polypeptide gene transcription. Biochem Biophys Res Commun 1996;229:746-51
  • Chakrabarti SK, James JC, Mirmira RG. Quantitative assessment of gene targeting in vitro and in vivo by the pancreatic transcription factor, Pdx1. J Biol Chem 2002;277:13286-93
  • Stoffers DA, Ferrer J, Clarke WL, Habener JF. Early-onset type-II diabetes mellitus (MODY4) linked to IPF1. Nat Genet 1997;17:138-9
  • Macfarlane WM, Frayling TM, Ellard S, et al. Missense mutations in the insulin promoter factor-1 gene predispose to type 2 diabetes. J Clin Invest 1999;104:R33-9
  • Hani EH, Stoffers DA, Chevre JC, et al. Defective mutations in the insulin promoter factor-1 (IPF-1) gene in late-onset type 2 diabetes mellitus. J Clin Invest 1999;104:R41-8
  • Serup P, Jensen J, Andersen FG, et al. Induction of insulin and islet amyloid polypeptide production in pancreatic islet glucagonoma cells by insulin promoter factor 1. Proc Natl Acad Sci USA 1996;93:9015-20
  • Watada H, Kajimoto Y, Miyagawa J, et al. PDX-1 induces insulin and glucokinase gene expressions in alphaTC1 clone 6 cells in the presence of betacellulin. Diabetes 1996;45:1826-31
  • Kojima H, Nakamura T, Fujita Y, et al. Combined expression of pancreatic duodenal homeobox 1 and islet factor 1 induces immature enterocytes to produce insulin. Diabetes 2002;51:1398-408
  • Yoshida S, Kajimoto Y, Yasuda T, et al. PDX-1 induces differentiation of intestinal epithelioid IEC-6 into insulin-producing cells. Diabetes 2002;51:2505-13
  • Ferber S, Halkin A, Cohen H, et al. Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia. Nat Med 2000;6:568-72
  • Heller RS, Stoffers DA, Bock T, et al. Improved glucose tolerance and acinar dysmorphogenesis by targeted expression of transcription factor PDX-1 to the exocrine pancreas. Diabetes 2001;50:1553-61
  • 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;15:444-54
  • Miyatsuka T, Kaneto H, Kajimoto Y, et al. Ectopically expressed PDX-1 in liver initiates endocrine and exocrine pancreas differentiation but causes dysmorphogenesis. Biochem Biophys Res Commun 2003;310:1017-25
  • Horb ME, Shen CN, Tosh D, Slack JM. Experimental conversion of liver to pancreas. Curr Biol 2003;13:105-15
  • Cao LZ, Tang DQ, Horb ME, et al. High glucose is necessary for complete maturation of Pdx1–VP16-expressing hepatic cells into functional insulin-producing cells. Diabetes 2004;53:3168-78
  • Kaneto H, Nakatani Y, Miyatsuka T, et al. PDX-1/VP16 fusion protein, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance. Diabetes 2005;54:1009-22
  • Imai J, Katagiri H, Yamada T, et al. Constitutively active PDX1 induced efficient insulin production in adult murine liver. Biochem Biophys Res Commun 2005;326:402-9
  • Wu H, MacFarlane WM, Tadayyon M, et al. Insulin stimulates pancreatic-duodenal homoeobox factor-1 (PDX1) DNA-binding activity and insulin promoter activity in pancreatic β cells. Biochem J 1999;344(Pt 3):813-8
  • Macfarlane WM, Shepherd RM, Cosgrove KE, et al. Glucose modulation of insulin mRNA levels is dependent on transcription factor PDX-1 and occurs independently of changes in intracellular Ca2+. Diabetes 2000;49:418-23
  • Elrick LJ, Docherty K. Phosphorylation-dependent nucleocytoplasmic shuttling of pancreatic duodenal homeobox-1. Diabetes 2001;50:2244-52
  • Gerrish K, Gannon M, Shih D, et al. Pancreatic β cell-specific transcription of the pdx-1 gene. The role of conserved upstream control regions and their hepatic nuclear factor 3β sites. J Biol Chem 2000;275:3485-92
  • Melloul D, Marshak S, Cerasi E. Regulation of pdx-1 gene expression. Diabetes 2002;51(Suppl 3):S320-5
  • Gerrish K, Cissell MA, Stein R. The role of hepatic nuclear factor 1α and PDX-1 in transcriptional regulation of the pdx-1 gene. J Biol Chem 2001;276:47775-84
  • Ben-Shushan E, Marshak S, Shoshkes M, et al. A pancreatic β-cell-specific enhancer in the human PDX-1 gene is regulated by hepatocyte nuclear factor 3β (HNF-3β), HNF-1α, and SPs transcription factors. J Biol Chem 2001;276:17533-40
  • Wu KL, Gannon M, Peshavaria M, et al. Hepatocyte nuclear factor 3β is involved in pancreatic β-cell-specific transcription of the pdx-1 gene. Mol Cell Biol 1997;17:6002-13
  • Samaras SE, Cissell MA, Gerrish K, et al. Conserved sequences in a tissue-specific regulatory region of the pdx-1 gene mediate transcription in pancreatic β cells: role for hepatocyte nuclear factor 3β and Pax6. Mol Cell Biol 2002;22:4702-13
  • Samaras SE, Zhao L, Means A, et al. The islet β cell-enriched RIPE3b1/Maf transcription factor regulates pdx-1 expression. J Biol Chem 2003;278:12263-70
  • Vanhoose AM, Samaras S, Artner I, et al. MafA and MafB regulate Pdx1 transcription through the Area II control region in pancreatic β cells. J Biol Chem 2008;283:22612-9
  • 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;258:105-16
  • Wiebe PO, Kormish JD, Roper VT, et al. 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;27:4093-104
  • Miyatsuka T, Matsuoka TA, Shiraiwa T, et al. Ptf1a and RBP-J cooperate in activating Pdx1 gene expression through binding to Area III. Biochem Biophys Res Commun 2007;362:905-9
  • 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;140:5374-81
  • Sharma A, Zangen DH, Reitz P, et al. The homeodomain protein IDX-1 increases after an early burst of proliferating during pancreatic regeneration. Diabetes 1999;48:507-13
  • Swift GH, Liu Y, Rose SD, et al. An endocrine-exocrine switch in the activity of the pancreatic homeodomain protein PDX1 through formation of a trimeric complex with PBX1b and MRG1 (MEIS2). Mol Cell Biol 1998;18:5109-20
  • Deramaudt TB, Sachdeva MM, Wescott MP, et al. The PDX1 homeodomain transcription factor negatively regulates the pancreatic ductal cell-specific keratin 19 promoter. J Biol Chem 2006;281:38385-95
  • Gmyr V, Kerr-Conte J, Belaich S, et al. Adult human cytokeratin 19-positive cells reexpress insulin promoter factor 1 in vitro: further evidence for pluripotent pancreatic stem cells in human. Diabetes 2000;49:1671-80
  • Song SY, Gannon M, Washington MK, et al. Expansion of Pdx1-expressing pancreatic epithelium and islet neogenesis in transgenic mice overexpressing transforming growth factor α. Gastroenterology 1999;117:1416-26
  • Koizumi M, Doi R, Toyoda E, et al. Increased PDX-1 expression is associated with outcome in patients with pancreatic cancer. Surgery 2003;134:260-6
  • Jensen JN, Cameron E, Garay MV, et al. Recapitulation of elements of embryonic development in adult mouse pancreatic regeneration. Gastroenterology 2005;128:728-41
  • Miyatsuka T, Kaneto H, Shiraiwa T, et al. Persistent expression of PDX-1 in the pancreas causes acinar-to-ductal metaplasia through Stat3 activation. Genes Dev 2006;20:1435-40
  • Sommer L, Ma Q, Anderson DJ. neurogenins, a novel family of atonal-related bHLH transcription factors, are putative mammalian neuronal determination genes that reveal progenitor cell heterogeneity in the developing CNS and PNS. Mol Cell Neurosci 1996;8:221-41
  • Schwitzgebel VM, Scheel DW, Conners JR, et al. Expression of neurogenin3 reveals an islet cell precursor population in the pancreas. Development 2000;127:3533-42
  • Jensen J, Heller RS, Funder-Nielsen T, et al. Independent development of pancreatic α- and α-cells from neurogenin3-expressing precursors: a role for the notch pathway in repression of premature differentiation. Diabetes 2000;49:163-76
  • Schonhoff SE, Giel-Moloney M, Leiter AB. Neurogenin 3-expressing progenitor cells in the gastrointestinal tract differentiate into both endocrine and non-endocrine cell types. Dev Biol 2004;270:443-54
  • 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;97:1607-11
  • Sosa-Pineda B, Chowdhury K, Torres M, et al. The Pax4 gene is essential for differentiation of insulin-producing β cells in the mammalian pancreas. Nature 1997;386:399-402
  • St-Onge L, Sosa-Pineda B, Chowdhury K, et al. Pax6 is required for differentiation of glucagon-producing α-cells in mouse pancreas. Nature 1997;387:406-9
  • Sander M, Neubuser A, Kalamaras J, et al. Genetic analysis reveals that PAX6 is required for normal transcription of pancreatic hormone genes and islet development. Genes Dev 1997;11:1662-73
  • Naya FJ, Huang HP, Qiu Y, et al. Diabetes, defective pancreatic morphogenesis, and abnormal enteroendocrine differentiation in BETA2/neuroD-deficient mice. Genes Dev 1997;11:2323-34
  • Huang HP, Liu M, El-Hodiri HM, et al. Regulation of the pancreatic islet-specific gene BETA2 (neuroD) by neurogenin 3. Mol Cell Biol 2000;20:3292-307
  • Smith SB, Gasa R, Watada H, et al. Neurogenin3 and hepatic nuclear factor 1 cooperate in activating pancreatic expression of Pax4. J Biol Chem 2003;278:38254-9
  • Watada H, Scheel DW, Leung J, German MS. Distinct gene expression programs function in progenitor and mature islet cells. J Biol Chem 2003;278:17130-40
  • Jenny M, Uhl C, Roche C, et al. Neurogenin3 is differentially required for endocrine cell fate specification in the intestinal and gastric epithelium. EMBO J 2002;21:6338-47
  • Lee CS, Perreault N, Brestelli JE, Kaestner KH. Neurogenin 3 is essential for the proper specification of gastric enteroendocrine cells and the maintenance of gastric epithelial cell identity. Genes Dev 2002;16:1488-97
  • Apelqvist A, Li H, Sommer L, et al. Notch signalling controls pancreatic cell differentiation. Nature 1999;400:877-81
  • Heremans Y, Van De Casteele M, In't Veld P, et al. Recapitulation of embryonic neuroendocrine differentiation in adult human pancreatic duct cells expressing neurogenin 3. J Cell Biol 2002;159:303-12
  • Gasa R, Mrejen C, Leachman N, et al. Proendocrine genes coordinate the pancreatic islet differentiation program in vitro Proc Natl Acad Sci USA 2004;101:13245-50
  • Ogihara T, Fujitani Y, Uchida T, et al. Combined expression of transcription factors induces AR42J-B13 cells to differentiate into insulin-producing cells. Endocr J 2008;55:691-8
  • Heitzler P, Simpson P. The choice of cell fate in the epidermis of Drosophila. Cell 1991;64:1083-92
  • Jensen J, Pedersen EE, Galante P, et al. Control of endodermal endocrine development by Hes-1. Nat Genet 2000;24:36-44
  • Sumazaki R, Shiojiri N, Isoyama S, et al. Conversion of biliary system to pancreatic tissue in Hes1-deficient mice. Nat Genet 2004;36:83-7
  • Fukuda A, Kawaguchi Y, Furuyama K, et al. Ectopic pancreas formation in Hes1-knockout mice reveals plasticity of endodermal progenitors of the gut, bile duct, and pancreas. J Clin Invest 2006;116:1484-93
  • Murtaugh LC, Stanger BZ, Kwan KM, Melton DA. Notch signaling controls multiple steps of pancreatic differentiation. Proc Natl Acad Sci USA 2003;100:14920-5
  • Hald J, Hjorth JP, German MS, et al. Activated Notch1 prevents differentiation of pancreatic acinar cells and attenuate endocrine development. Dev Biol 2003;260:426-37
  • Lee JC, Smith SB, Watada H, et al. Regulation of the pancreatic pro-endocrine gene neurogenin3. Diabetes 2001;50:928-36
  • Smith SB, Watada H, German MS. Neurogenin3 activates the islet differentiation program while repressing its own expression. Mol Endocrinol 2004;18:142-9
  • Bonner-Weir S, Taneja M, Weir GC, et al. In vitro cultivation of human islets from expanded ductal tissue. Proc Natl Acad Sci USA 2000;97:7999-8004
  • Zulewski H, Abraham EJ, Gerlach MJ, et al. Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes 2001;50:521-33
  • Seaberg RM, Smukler SR, Kieffer TJ, et al. Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat Biotechnol 2004;22:1115-24
  • Suzuki A, Nakauchi H, Taniguchi H. Prospective isolation of multipotent pancreatic progenitors using flow-cytometric cell sorting. Diabetes 2004;53:2143-52
  • Lee CS, De Leon DD, Kaestner KH, Stoffers DA. Regeneration of pancreatic islets after partial pancreatectomy in mice does not involve the reactivation of neurogenin-3. Diabetes 2006;55:269-72
  • Nir T, Melton DA, Dor Y. Recovery from diabetes in mice by β cell regeneration. J Clin Invest 2007;117:2553-61
  • Dor Y, Brown J, Martinez OI, Melton DA. Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation. Nature 2004;429:41-6
  • Brennand K, Huangfu D, Melton D. All β cells contribute equally to islet growth and maintenance. PLoS Biol 2007;5:e163. Published online 2007 May 29, doi:10.1371/journal.pbio.0050163
  • Teta M, Rankin MM, Long SY, et al. Growth and regeneration of adult β cells does not involve specialized progenitors. Dev Cell 2007;12:817-26
  • Xu X, D'Hoker J, Stange G, et al. β cells can be generated from endogenous progenitors in injured adult mouse pancreas. Cell 2008;132:197-207
  • Sharma A, Stein R. Glucose-induced transcription of the insulin gene is mediated by factors required for β-cell-type-specific expression. Mol Cell Biol 1994;14:871-9
  • Olbrot M, Rud J, Moss LG, Sharma A. Identification of β-cell-specific insulin gene transcription factor RIPE3b1 as mammalian MafA. Proc Natl Acad Sci USA 2002;99:6737-42
  • Kataoka K, Han SI, Shioda S, et al. MafA is a glucose-regulated and pancreatic β-cell-specific transcriptional activator for the insulin gene. J Biol Chem 2002;277:49903-10
  • Matsuoka TA, Zhao L, Artner I, et al. Members of the large Maf transcription family regulate insulin gene transcription in islet β cells. Mol Cell Biol 2003;23:6049-62
  • Matsuoka TA, Artner I, Henderson E, et al. The MafA transcription factor appears to be responsible for tissue-specific expression of insulin. Proc Natl Acad Sci USA 2004;101:2930-3
  • Zhang C, Moriguchi T, Kajihara M, et al. MafA is a key regulator of glucose-stimulated insulin secretion. Mol Cell Biol 2005;25:4969-76
  • Matsuoka TA, Kaneto H, Stein R, et al. MafA regulates expression of genes important to islet β-cell function. Mol Endocrinol 2007;21:2764-74
  • Kaneto H, Matsuoka TA, Nakatani Y, et al. A crucial role of MafA as a novel therapeutic target for diabetes. J Biol Chem 2005;280:15047-52
  • Harrison KA, Thaler J, Pfaff SL, et al. Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9-deficient mice. Nat Genet 1999;23:71-5
  • 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
  • Krapp A, Knofler M, Ledermann B, et al. 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;12:3752-63
  • Sellick GS, Barker KT, Stolte-Dijkstra I, et al. Mutations in PTF1A cause pancreatic and cerebellar agenesis. Nat Genet 2004;36:1301-5
  • Kawaguchi Y, Cooper B, Gannon M, et al. The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nat Genet 2002;32:128-34
  • Obata J, Yano M, Mimura H, et al. p48 subunit of mouse PTF1 binds to RBP-Jκ/CBF-1, the intracellular mediator of Notch signalling, and is expressed in the neural tube of early stage embryos. Genes Cells 2001;6:345-60
  • Beres TM, Masui T, Swift GH, et al. 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;26:117-30
  • Seymour PA, Freude KK, Tran MN, et al. SOX9 is required for maintenance of the pancreatic progenitor cell pool. Proc Natl Acad Sci USA 2007;104:1865-70
  • Lynn FC, Smith SB, Wilson ME, et al. Sox9 coordinates a transcriptional network in pancreatic progenitor cells. Proc Natl Acad Sci USA 2007;104:10500-5
  • Sussel L, Kalamaras J, Hartigan-O'Connor DJ, et al. Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to arrested differentiation of pancreatic β cells. Development 1998;125:2213-21
  • Sander M, Sussel L, Conners J, et al. Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of β-cell formation in the pancreas. Development 2000;127:5533-40
  • Prado CL, Pugh-Bernard AE, Elghazi L, et al. Ghrelin cells replace insulin-producing β cells in two mouse models of pancreas development. Proc Natl Acad Sci USA 2004;101:2924-9
  • Ahlgren U, Pfaff SL, Jessell TM, et al. Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells. Nature 1997;385:257-60
  • Fujitani Y, Kajimoto Y, Yasuda T, et al. 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;19:8281-91
  • 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;19:8272-80
  • Collombat P, Mansouri A, Hecksher-Sorensen J, et al. Opposing actions of Arx and Pax4 in endocrine pancreas development. Genes Dev 2003;17:2591-603
  • Schwarze SR, Ho A, Vocero-Akbani A, Dowdy SF. In vivo protein transduction: delivery of a biologically active protein into the mouse. Science 1999;285:1569-72
  • Gump JM, Dowdy SF. TAT transduction: the molecular mechanism and therapeutic prospects. Trends Mol Med 2007;13:443-8
  • Sugita T, Yoshikawa T, Mukai Y, et al. Comparative study on transduction and toxicity of protein transduction domains. Br J Pharmacol 2008;153:1143-52
  • 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;52:1732-7
  • Noguchi H, Matsushita M, Matsumoto S, et al. Mechanism of PDX-1 protein transduction. Biochem Biophys Res Commun 2005;332:68-74
  • Noguchi H, Bonner-Weir S, Wei FY, et al. BETA2/NeuroD protein can be transduced into cells due to an arginine- and lysine-rich sequence. Diabetes 2005;54:2859-66
  • Dominguez-Bendala J, Klein D, Ribeiro M, et al. TAT-mediated neurogenin 3 protein transduction stimulates pancreatic endocrine differentiation in vitro. Diabetes 2005;54:720-6

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.