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1.2.7 Literatur
Ahlgren U, Jonsson J, Edlund H (1996) The morphogenesis of the pancreatic mesenchyme is uncoupled from that of the pancreatic epithelium in IPF1/PDX1-deficient mice. Development 122: 1409–1416
Ahlgren U, Pfaff SL, Jessell T, Edlund T, Edlund H (1997) Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells. Nature 385: 257–260
Ahlgren U, Jonsson J, Jonsson L, Simu K, Edlund H (1998) β-cell-specific inactivation of the mouse Ipf1/Pdxl gene results in loss of the β-cell phenotype and the maturity onset diabetes. Genes Dev 12: 1763–1768
Alpert S, Hanahan D, Teitelman G (1988) Hybrid insulin genes reveal a developmental lineage for pancreatic endocrine cells and imply a relationship with neurons. Cell 53: 295–308
Andersen FG, Heller RS, Petersen HV, Jensen J, Madsen OD, Serup P (1999 a) Pax6 and Cdx2/3 form a functional complex on the rat glucagon gene promoter G1-element. FEBS Letters 445: 306–310
Andersen FG, Jensen J, Heller RS, Petersen HV, Larsson LI, Madsen OD, Serup P (1999b) Pax6 and Pdx1 form a functional complex on the rat somatostatin gene up-stream enhancer. FEBS Letters 445: 315–320
Ang SL, Rossant J (1994) HNF-3β is essential for node and notochord formation in mouse development. Cell 78: 561–574
Apelqvist A, Li H, Sommer L et al. (1999) Notch signalling controls pancreatic cell differentiation. Nature 400: 877–881
Aqelqvist A, Ahlgren U, Edlund H (1997) Sonic hedgehog directs specialised mesoderm differentiation in the intestine and pancreas. Curr Biol 7: 801–804
Arnush M, Gu D, Baugh C, Sawyer SP, Mroczkowski B, Krahl T, Sarvetnick N (1996) Growth factors in the regenerating pancreas of gamma-interferon transgenic mice. Lab Invest 74: 985–990
Assady S, Maor G, Amit M, Itskovitz-Eldor J, Skorecki KL, Tzukerman M (2001) Insulin production by human embryonic stem cells. Diabetes 50: 1691–1697
Bach F, Fishman J, Daniels N et al. (1998) Uncertainty in xenotransplantation: Individual benefit versus collective risk. Nature Med 4: 141–144
Beattie G, Itkin-Ansari P, Cirulli V et al. (1999) Sustained proliferation of PDX-1+ cells derived from human islets. Diabetes 48: 1013–1019
Bell GI, Xiang KS, Newman MV et al. (1991) Gene for non-insulin-dependent diabetes mellitus (maturity-onset diabetes of the young subtype) is linked to DNA polymorphism on human chromosome 20q. Proc Natl Acad Sci USA 88: 1484–1488
Bernal-Mizrachi E, Wen W, Stahlhut S, Welling CM, Permutt MA (2001) Islet β cell expression of constitutively active Akt1/PKB α induces striking hypertrophy, hyperplasia, and hyperinsulinemia. J Clin Invest 108: 1631–1638
Bhushan A, Itoh N, Kato S, Thiery JP, Czernichow P, Bellusci S, Scharfmann R (2001) Fgf10 is essential for maintaining the proliferative capacity of epithelial progenitor cells during early pancreatic organogenesis. Development 128: 5109–5117
Blyszczuk P, Czyz J, Kania G, Wagner M, Roll U, St-Onge L, Wobus AM (2003) Expression of Pax4 in embryonic stem cells promotes differentiation of nestin-positive progenitor and insulin-producing cells. Proc Natl Acad Sci USA 100: 998–1003
Bocian-Sobkowska J, Zabel M, Wozniak W, Surdyk-Zasada J (1997) Prenatal development of the human pancreatic islets. Immunocytochemical identification of insulin-, glucagon-, somatostatin-and pancreatic polypeptide-containing cells. Folia Histochem Cytobiol 35: 151–154
Boj SF, Parrizas M, Maestro MA, Ferrer J (2001) A transcription factor regulatory circuit in differentiated pancreatic cells. Proc Natl Acad Sci USA 98: 14481–14486
Bonner-Weir S, Trent DF, Weir GC (1983) Partial pancreatectomy in the rat and subsequent defect in glucose-induced insulin release. J Clin Invest 71: 1544–1553
Bonner-Weir S, Baxter LA, Schuppin GT, Smith FE (1993) A second pathway for regeneration of adult exocrine and endocrine pancreas. A possible recapitulation of embryonic development. Diabetes 42: 1715–1720
Bonner-Weir S, Stubbs M, Reitz P, Taneja M, Smith FE (1997) Partial pancreatectomy as a model of pancreatic regeneration. In: Sarvetnick N (ed) Pancreatic growth and regeneration. Karger, New York, pp 138–153
Bonner-Weir S, Taneja M, Weir GC, Tatarkiewicz K, Song KH, Sharma A, O’Neil JJ (2000) In vitro cultivation of human islets from expanded ductal tissue. Proc Natl Acad Sci USA 97: 7999–8004
Bosco D, Meda P, Halban PA, Rouiller DG (2000) Importance of cell-matrix interactions in rat islet β-cell secretion in vitro — Role of α6 β1 integrin. Diabetes 49: 233–243
Bottinger EP, Jakubczak JL, Roberts ISD et al. (1997) Expression of a dominant-negative mutant Tgf-β type II Receptor in transgenic mice reveals essential roles for Tgf-β in Regulation of growth and differentiation in the exocrine pancreas. EMBO J 16: 2621–2633
Bouwens L, Pipeleers DG (1998) Extra-insular β-cells associated with ductules are frequent in adult human pancreas. Diabetologia 41: 629–633
Bouwens L, Lu WG, De Krijger R (1997) Proliferation and differentiation in the human fetal endocrine pancreas. Diabetologia 40: 398–404
Brelje TC, Scharp DW, Lacy PE et al. (1993) Effect of homologous placental lactogens, prolactins, and growth hormones on islet B-cell division and insulin secretion in rat, mouse, and human islets: Implication for placental lactogen regulation of islet function during pregnancy. Endocrinology 132: 879–887
Butler D, Wadman M, Lehrman S, Schiermeier Q (1998) Last chance to stop and think on risks of xenotransplants. Nature 391: 320–324
Byrne MM et al. (1996) Altered insulin secretory responses to glucose in diabetic and nondiabetic subjects with mutations in the diabetes susceptibility gene M0DY3 on chromosome 12. Diabetes 45: 1503–1510
Cederholm J, Wibell L (1985) Evaluation of insulin release and relative peripheral resistance with use of the oral glucose tolerance test: A study in subjects with normoglycaemia, glucose intolerance and non-insulin-dependent diabetes mellitus. Scand J Clin Lab Invest 45: 741–751
Cho H et al. (2001) Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB β). Science 292: 1728–1731
Cirulli V et al. (1998) Ksa antigen ep-cam mediates cell-cell adhesion of pancreatic epithelial cells — Morphoregulatory roles in pancreatic islet development. J Cell Biol 140: 1519–1534
Cirulli V et al. (2000) Expression and function of α(v)β(3) and α(v)β(5) integrins in the developing pancreas: Roles in the adhesion and migration of putative endocrine progenitor cells. J Cell Biol 150: 1445–1459
Clatworthy JP, Subramanian V (2001) Stem cells and the regulation of proliferation, differentiation and patterning in the intestinal epithelium: Emerging insights from gene expression patterns, transgenic and gene ablation studies. Mech Devel 101: 3–9
Collombat P, Mansouri A, Hecksher-Sorensen J, Serup P, Krull J, Gradwohl G, Gruss P (2003) Opposing actions of Arx and Pax4 in endocrine pancreas development. Genes Dev 17: 2591–2603
Czyz J, Wiese C, Rolletschek A, Blyszczuk P, Cross M, Wobus AM (2003) Potential of embryonic and adult stem cells in vitro. Biol Chem 384: 1391–1409
Dahl U, Sjödin A, Semb H (1996) Cadherins regulate aggregation of pancreatic β-cells in vivo. Development 122: 2895–2902
Deltour L, Leduque P, Paldi A, Ripoche MA, Dubois P, Jami J (1991) Polyclonal origin of pancreatic islets in aggregation mouse chimaeras. Development 112: 1115–1121
Deutsch G, Jung JN, Zheng MH, Lora J, Zaret KS (2001) A bipotential precursor population for pancreas and liver within the embryonic endoderm. Development 128: 871–881
Dukes ID et al. (1998) Defective pancreatic β-cell glycolytic signaling in hepatocyte nuclear factor-1α-deficient mice. J Biol Chem 273: 24457–24464
Duncan S, Angeles Navas M, Dufort D, Rossant J, Stoffel M (1998) Regulation of a transcription factor network required for differentiation and metabolism. Science 281: 692–695
Dutta S, Gannon M, Peers B, Wright C, Bonner-Weir S, Montminy M (2001) PDX: PBX complexes are required for normal proliferation of pancreatic cells during development. Proc Natl Acad Sci USA 98: 1065–1070
Elrick LJ, Docherty K (2001) Phosphorylation-dependent nucleocytoplasmic shuttling of pancreatic duodenal homeobox-1. Diabetes 50: 2244–2252
Esni F, Johansson BR, Radice GL, Semb H (2001) Dorsal pancreas agenesis in N-cadherin-deficient mice. Dev Biol 238: 202–212
Fajans SS (1990) Scope and heterogeneous nature of MODY. Diabetes Care 13: 49–64
Fajans SS, Bell GI, Polonsky KS (2001) Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. N Engl J Med 345: 971–980
Fausto N (2000) Liver regeneration. J Hepatol 32: 19–31
Fausto N (2001) Liver regeneration: from laboratory to clinic. Liver Transplant 7: 835–44
Ferber S et al. (2000) Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia. Nature Med 6: 568–572
Fernandes A, King LC, Guz Y, Stein R, Wright CV, Teitelman G (1997) Differentiation of new insulin-producing cells is induced by injury in adult pancreatic islets. Endocrinology 138: 1750–1762
Field HA, Dong PDS, Beis D, Stainier DYR (2003) Formation of the digestive system in zebrafish. II: Pancreas morphogenesis. Dev Biol 261: 197–208
Flock G, Drucker DJ (2002) Pax-2 activates the proglucagon gene promoter but is not essential for proglucagon gene expression or development of proglucagon-producing cell lineages in the murine pancreas or intestine. Mol Endocrinol 16: 2349–2359
Fontaine J, Le Douarin NM (1977 a) Analysis of endoderm formation in the avian blastoderm by the use of quail-chick chimaeras. The problem of the neurectodermal origin of the cells of the APUD series. J Embryol Experiment Morphol 41: 209–222
Fontaine J, Le Lievre C, Le Douarin NM (1977b) What is the developmental fate of the neural crest cells which migrate into the pancreas in the avian embryo? Gen Comp Endocrinol 33: 394–404
Froguel P et al. (1992) Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin-dependent diabetes mellitus. Nature 356: 162–164
Fuchs E, Segre JA (2000) Stem cells: A new lease on life. Cell 100: 143–155
Gerrish K, Grannon M, Shih D et al. (2000) 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 275: 3485–3492
Gershon D (2003) Complex political, ethical and legal issues surround research on human embryonic stem cells. Nature 422: 928–929
Gittes GK, Galante PE, Hanahan D, Rutter WJ, Debas HT (1996) Lineage-specific morphogenesis in the developing pancreas: Role of mesenchymal factors. Development 122: 439–447
Gradwohl G, Dierich A, LeMeur MFG (2000) Neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas. Proc Natl Acad Sci USA 97: 1607–1611
Gragnoli C, Lindner T, Cockburn BN, Kaisaki PJ, Gragnoli F, Marozzi G, Bell GI (1997) Maturity-onset diabetes of the young due to a mutation in the hepatocyte nuclear factor-4α binding site in the promoter of the hepatocyte nuclear factor-1α gene. Diabetes 46: 1648–1651
Grapin-Botton A, Majithia AR, Melton DA (2001) Key events of pancreas formation are triggered in gut endoderm by ectopic expression of pancreatic regulatory genes. Genes Dev 15: 444–454
Group TDCaCTR (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Eng J Med 329: 977–986
Gu D, Sarvetnick N (1993) Epithelial cell proliferation and islet neogenesis in IFN-γ transgenic mice. Development 118: 33–46
Gu D, Lee M, Krahl T, Sarvetnick N (1994) Transitional cells in the regenerating pancreas. Development 120: 1873–1881
Gu D, Arnush M, Sawyer SP, Sarvetnick N (1995) Transgenic mice expressing IFN-γ in pancreatic β-cells are resistant to streptozotocin-induced diabetes. Am J Physiol 269: E1089–1094
Gu GQ, Dubauskaite J, Melton DA, Fishman MP (2002) Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development 129: 2447–2457
Gu GQ, Brown JR, Melton DA (2003) Direct lineage tracing reveals the ontogeny of pancreatic cell fates during mouse embryogenesis. Mechanisms of Development 120: 35–43
Guz Y, Montminy MR, Stein R, Loenard J, Gamer LW, Wright CVE, Teitelman G (1995) Expression of murine STF-1, a putative insulin gene transcription factor, in β-cells of pancreas, duodenal epithelium and pancreatic exocrine and endocrine progenitors during ontogeny. Development 121: 11–18
Hahn von Dorsche H, Reiher H, Hahn HJ (1988) Phases in the early development of the human islet organ. Anat Anz 166: 69–76
Halban PA, Kahn SE, Lernmark A, Rhodes CJ (2001) Gene and cell-replacement therapy in the treatment of type 1 diabetes — How high must the standards be set? Diabetes 50: 2181–2191
Hald J, Hjorth JP, German MS, Madsen OD, Serup P, Jensen J (2003) Activated Notch1 prevents differentiation of pancreatic acinar cells and attenuate endocrine development. Dev Biol 260: 426–437
Halvorsen TL, Beattie GM, Lopez AD, Hayek A, Levine F (2000) Accelerated telomere shortening and senescence in human pancreatic islet cells stimulated to divide in vitro. J Endocrinol 166: 103–109
Hardikar AA, Karandikar MS, Bhonde RR (1999) Effect of partial pancreatectomy on diabetic status in BALB/c mice. J Endocrinol 162: 189–195
Harrison KA, Thaler J, Pfaff SL, Gu H, Kehrl JH (1999) Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9-deficient mice. Nature Genet 23: 71–75
Hart A, Papadopoulou S, Edlund H (2003) Fgf10 maintains notch activation, stimulates proliferation, and blocks differentiation of pancreatic epithelial cells. Dev Dyn 228: 185–193
Hebrok M, Kim S, Melton D (1998) Notochord repression of endodermal Sonic hedgehog permits pancreas development. Genes Dev 12: 1705–1713
Hebrok M, Kim SK, St-Jacques B, McMahon AP, Melton DA (2000) Regulation of pancreas development by hedgehog signaling. Development 127: 4905–4913
Herrera PL (2000) Adult insulin-and glucagon-producing cells differentiate from two independent cell lineages. Development 127: 2317–2322
Hirshberg B, Rother KI, Digon BJ, Venstrom J, Harlan DM (2003) State of the art: Islet transplantation for the cure of type 1 diabetes mellitus. Rev Endocr Metab Disord 4: 381–389
Hori Y, Rulifson IC, Tsai BC, Heit JJ, Cahoy JD, Kim SK (2002) Growth inhibitors promote differentiation of insulin-producing tissue from embryonic stem cells. Proc Natl Acad Sci USA 99: 16105–16110
Huang HP, Liu M, El-Hodiri HM, Chu K, Jamrich M, Tsai MJ (2000) Regulation of the pancreatic islet-specific gene BETA2 (neuroD) by neurogenin 3. Mol Cell Biol 20: 3292–3307
Hussain MA, Miller CP, Habener JF (2002) Brn-4 transcription factor expression targeted to the early developing mouse pancreas induces ectopic glucagon gene expression in insulin-producing β cells. J Biol Chem 277: 16028–16032
Ianus A, Holz GG, Theise ND, Hussain MA (2003) In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest 111: 843–850
Ingham P, McMahon A (2001) Hedgehog signaling in animal development: Paradigms and principles. Genes Dev 15: 3059–3087
Jackson K, Mi T, Goodell M (1999) Hematopoietic potential of stem cells isolated from murine skeletal muscle. Proc Natl Acad Sci USA 96: 14482–14486
Jacquemin P et al. (2000) Transcription factor hepatocyte nuclear factor 6 regulates pancreatic endocrine cell differentiation and controls expression of the proendocrine gene ngn3. Mol Cell Biol 20: 4445–4454
Jensen J et al. (2000 a) Control of endodermal endocrine development by Hes-1. Nature Genet 24: 36–44
Jensen J, Heller RS, Funder-Nielsen T et al. (2000 b) Independent development of pancreatic α-and β-cells from neurogenin3-expressing precursors: A role for the notch pathway in repression of premature differentiation. Diabetes 49: 163–176
Johnson DD, Palumbo PJ, Chu CP (1980) Diabetic ketoacidosis in a community-based population. Mayo Clin Proc 55: 83–88
Johnson JD, Ahmed NT, Luciani DS et al. (2003) Increased islet apoptosis in Pdx1(+/−) mice. J Clin Invest 111: 1147–1160
Jonsson J, Carlsson L, Edlund T, Edlund H (1994) Insulin-promoter-factor 1 is required for pancreas development in mice. Nature 371: 606–609
Kaestner KH et al. (2003) Transcriptional program of the endocrine pancreas in mice and humans. Diabetes 52: 1604–1610
Kantengwa S, Baetens D, Sadoul K, Buck CA, Halban PA, Rouiller DG (1997) Identification and Characterization of α-3-β-l Integrin on Primary and Transformed Rat Islet Cells. Exp Cell Res 237: 394–402
Kawaguchi Y, Cooper B, Gannon M, Ray M, MacDonald RJ, Wright CVE (2002) The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nature Genet 32: 128–134
Kelly OG, Melton DA (2000) Development of the pancreas in Xenopus laevis. Dev Dyn 218: 615–627
Kerr-Conte J, Pattou F, Lecomte-Houcke M, Xia Y, Boilly B, Proye C, Lefebvre J (1996) Ductal cyst formation in collagen-embedded adult human islet preparations. A means to the reproduction of nesidioblastosis in vitro. Diabetes 45: 1108–1114
Kim S, Melton D (1998) Pancreas development is promoted by cyclopamine, a hedgehog signaling inhibitor. Proc Natl Acad Sci USA 95: 13036–13041
Kim S, Hebrok M, Melton D (1997 a) Notochord to endoderm signaling is required for pancreas development. Development 124: 4243–4252
Kim S, Hebrok M, Melton D (1997b) Pancreas development in the chick embryo. Cold Spring Harbor Symp Quant Biol 62: 377–383
Kim SK, Hebrok M, Li E, Oh SP, Schrewe H, Harmon EB, Lee JS, Melton DA (2000) Activin receptor patterning of foregut organogenesis. Genes Dev 14: 1866–1871
Kim SK, Selleri L, Lee JS, Zhang AY, Gu XY, Jacobs Y, Cleary ML (2002) Pbx1 inactivation disrupts pancreas development and in Ipf1-deficient mice promotes diabetes mellitus. Nature Genet 30: 430–435
Kojima H, Fujimiya M, Matsumura K, Younan P, Imaeda H, Maeda M, Chan L (2003) NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice. Nature Med 9: 596–603
Krakowski ML, Kritzik MR, Jones EM et al. (1999) Transgenic expression of epidermal growth factor and keratinocyte growth factor in β-cells results in substantial morphological changes. J Endocrinol 162: 167–175
Krakowski M, Yeung B, Abdelmalik R et al. (2000) IFN-γ overexpression within the pancreas is not sufficient to rescue Pax4, Pax6, and Pdx-1 mutant mice from death. Pancreas 21: 399–406
Krapp A, Knofler M, Frutiger S, Hughes GJ, Hagenbuchle O, Wellauer PK (1996) The P48 DNA-Binding Subunit of Transcription Factor Ptf1 Is a New Exocrine Pancreas-Specific Basic Helix-Loop-Helix Protein. EMBO J 15: 4317–4329
Krapp A, Knofler M, Ledermann B et al. (1998) The bHLH protein PTF1-p48 is essential for the formation of the exocrine and the correct spatial organization of the endocrine pancreas. Genes Dev 12: 3752–3763
Kritzik M, Krahl T, Good A et al. (2000) Transcription factor expression during pancreatic islet regeneration. Mol Cell Endocrinol 164: 99–107
Kumar M, Jordan N, Melton D, Grapin-Botton A (2003) Signals from lateral plate mesoderm instruct endoderm toward a pancreatic fate. Dev Biol 259: 109–122
Kuzuya T, Matsuda A (1997) Classification of diabetes on the basis of etiologies versus degree of insulin deficiency. Diabetes Care 20: 219–220
Lakey JRT, Burridge PW, Shapiro AMJ (2003) Technical aspects of islet preparation and transplantation. Transpl Int 16: 613–632
Lammert E, Brown J, Melton DA (2000) Notch gene expression during pancreatic organogenesis. Mech Dev 94: 199–203
Le Bras S, Miralles F, Basmaciogullari A, Czernichow P, Scharfmann R (1998) Fibroblast growth factor 2 promotes pancreatic epithelial cell proliferation via functional fibroblast growth factor receptors during embryonic life. Diabetes 47: 1236–1242
Le Douarin NM (1988) On the origin of pancreatic endocrine cells. Cell 53: 169–171
Lee CS, Sund NJ, Vatamaniuk MZ, Matschinsky FM, Stoffers DA, Kaestner KH (2002) Foxa2 controls Pdx1 gene expression in pancreatic β-cells in vivo. Diabetes 51: 2546–2551
Lee JC, Smith SB, Watada H, Lin J, Scheel D, Wang JH, Mirmira RG, German MS (2001) Regulation of the pancreatic pro-endocrine gene neurogenin3. Diabetes 50: 928–936
Lefebvre VH, Otonkoski T, Ustinov J, Huotari MA, Pipeleers DG, Bouwens L (1998) Culture of adult human islet preparations with hepatocyte growth factor and 804G matrix is mitogenic for duct cells but not for β-cells. Diabetes 47: 134–137
Leonard R, Lazarow A, Od H (1973) Pancreatic islet transplantation in the rat. Diabetes 22: 413–428
Levine F, Leibowitz G (1999) Towards gene therapy of diabetes mellitus. Mol Med Today 5: 165–171
Li H, Arber S, Jessell T, Edlund H (1999) Selective agenesis of the dorsal pancreas in mice lacking homeobox gene Hlxb9. Nature Genet 23: 67–70
Li H, Edlund H (2001) Persistent expression of Hlxb9 in the pancreatic epithelium impairs pancreatic development. Dev Biol 240: 247–253
Like AA (1985) Spontaneous diabetes in animals. In: Wolk BW (ed) The diabetic pancreas, 2nd edn. Plenum Press, New York, pp 385–413
Lillioja S, Mott DM, Spraul M et al. (1993) Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians. N Engl J Med 329: 1988–1992
Litingtung Y, Lei L, Westphal H, Chiang C (1998) Sonic hedgehog is essential to foregut development. Nature Genet 20: 58–61
Lumelsky, Blondel O, Laeng P, Velasco I, Ravin R, McKay R (2001) Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 292: 1389–1394
Macfarlane WM, McKinnon CM, Felton-Edkins ZA, Cragg H, James RFL, Docherty K (1999) Glucose stimulates translocation of the homeodomain transcription factor PDX1 from the cytoplasm to the nucleus in pancreatic β-cells. J Biol Chem 274: 1011–1016
Malecki MT et al. (1999) Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Nat Genet 23: 323–328
Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 78: 7634–7638
McClenaghan NH, Flatt PR (1999) Engineering cultured insulin-secreting pancreatic B-cell lines. J Mol Med 77: 235–243
Miettinen PJ, Huotari MA, Koivisto T et al. (2000) Impaired migration and delayed differentiation of pancreatic islet cells in mice lacking EGF-receptors. Development 127: 2617–2627
Millen SK (1989) Einstein. Albert Einstein College of Medicine, Bronx, NY
Miller C, McGehee R, JF H (1994) IDX-1: A new homeodomain transcription factor expressed in rat pancreatic islets and duodenum that transactivates the somatostatin gene. EMBO J 13: 1145–1156
Miralles F, Battelino T, Czernichow P, Scharfmann R (1998 a) Tgf-β plays a key role in morphogenesis of the pancreatic islets of Langerhans by controlling the activity of the matrix metalloproteinase Mmp-2. J Cell Biol 143: 827–836
Miralles F, Czernichow P, Scharfmann R (1998b) Follistatin regulates the relative proportions of endocrine versus exocrine tissue during pancreatic development. Development 125: 1017–1024
Miralles F, Czernichow P, Ozaki K, Itoh N, Scharfmann R (1999) Signaling through fibroblast growth factor receptor 2β plays a key role in the development of the exocrine pancreas. Proc Natl Acad Sci USA 96: 6297–6272
Nagy A, Rossant J, Nagy R, Abramow-Newerly W, Roder J (1993) Derivation of completely cell culture-derived mice from early-passage embryonic stem cells. Proc Natl Acad Sci USA 90: 8424–8428
Nam Y, Aster JC, Blacklow SC (2002) Notch signaling as a therapeutic target. Curr Opin Chem Biol 6: 501–509
Naya F, Huang H-P, Qiu Y, Mutoh H, DeMayo F, Leiter A, Tsai M-J (1997) Diabetes, defective pancreatic morphogenesis and abnormal enteroendocrine differentiation in BETA2/NeuroD-deficient mice. Genes Dev 11: 2323–2334
Nielsen JH, Galsgaard ED, Moldrup A et al. (2001) Regulation of β-cell mass by hormones and growth factors. Diabetes 50(Suppl 1): S25–S29
Njolstad PR et al. (2001) Neonatal diabetes mellitus due to complete glucokinase deficiency. N Engl J Med 344: 1588–1592
Ober EA, Field HA, Stainier DYR (2003) From endoderm formation to liver and pancreas development in zebra-fish. Mech Dev 120: 5–18
Offield M, Jetton T, Labosky P et al. (1996) PDX-1 is required for pancreatic outgrowth and differentiation of the rostal duodenum. Development 122: 983–995
Ohlsson H, Karlsson K, Edlund T (1993) IPF1, a homeodomain-containing transactivator of the insulin gene. EMBO J 12: 4251–4259
Orci L (1982) Macro-and micro-domains in the endocrine pancreas. Diabetes 31: 538–565
Orci L, Unger RH (1975) Functional subdivision of islets of Langerhans and possible role of D cells. Lancet 2: 1243–1244
Pearse AG (1969) The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series and the embryologic, physiologic and pathologic implications of the concept. J Histochem Cytochem 17: 303–313
Pearse AG (1973) Cell migration and the alimentary system: Endocrine contributions of the neural crest to the gut and its derivatives. Digestion 8: 372–385
Pearse AG (1982) Islet cell precursors are neurones. Nature 295: 96–97
Pearse AG, Polak JM (1971) Neural crest origin of the endocrine polypeptide (APUD) cells of the gastrointestinal tract and pancreas. Gut 12: 783–788
Pearse AG, Polak JM, Heath CM (1973) Development, differentiation and derivation of the endocrine polypeptide cells of the mouse pancreas. Immunofluorescence, cytochemical and ultrastructural studies. Diabetologia 9: 120–129
Pearson ER et al. (2001) β-cell genes and diabetes: Quantitative and qualitative differences in the pathophysiology of hepatic nuclear factor-lα and glucokinase mutations. Diabetes 50(Suppl 1): S101–S107
Peers B, Sharma S, Johnson T, Kamps M, Montminy M (1995) The pancreatic islet factor Stf-1 binds cooperatively with Pbx to a regulatory element in the somatostatin promoter — Importance of the Fpwmk motif and of the homeodomain. Mol Cell Biol 15: 7091–7097
Petropavlovskaia M, Rosenberg L (2002) Identification and characterization of small cells in the adult pancreas: potential progenitor cells? Cell Tissue Res 310: 51–58
Pictet RL, Rall LB, Phelps P, Rutter WJ (1976) The neural crest and the origin of the insulin-producing and other gastrointestinal hormone-producing cells. Sci 191: 191–192
Pipeleers D (1987) The biosociology of pancreatic B cells. Diabetologia 30: 277–291
Polak M, Bouchareb-Banaei L, Scharfmann R, Czernichow P (2000) Early pattern of differentiation in the human pancreas. Diabetes 49: 225–232
Pulkkinen MA, Spencer-Dene B, Dickson C, Otonkoski T (2003) The IIIb isoform of fibroblast growth factor receptor 2 is required for proper growth and branching of pancreatic ductal epithelium but not for differentiation of exocrine or endocrine cells. Mech Dev 120: 167–175
Rafiq I, Kennedy HJ, Rutter GA (1998) Glucose-Dependent translocation of insulin promoter factor-1 (Ipf-1) between the nuclear periphery and the nucleoplasm of single Min6 β-Cells. J Biol Chem 273: 23241–23247
Rafiq I, Xavier GD, Hooper S, Rutter GA (2000) Glucose-stimulated preproinsulin gene expression and nuclear trans-location of pancreatic duodenum homeobox-1 require activation of phosphatidylinositol 3-kinase but not p38 MAP/SAPK2. J Biol Chem 275: 15977–15984
Rajagopal J, Anderson WJ, Kume S, Martinez OI, Melton DA (2003) Insulin staining of ES cell progeny from insulin uptake. Science 299: 17
Ramalho-Santos M, Melton DA, McMahon AP (2000) Hedgehog signals regulate multiple aspects of gastrointestinal development. Development 127: 2763–2772
Ramiya VK, Maraist M, Arfors KE, Schatz DA, Peck AB, Cornelius JG (2000) Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nature Med 6: 278–282
Rao MS et al. (1989) Role of periductal and ductular epithelial cells of the adult rat pancreas in pancreatic hepatocyte lineage. A change in the differentiation commitment. Am J Pathol 134: 1069–1086
Rausa F, Samadani U, Ye HG et al. (1997) The cut-homeodomain transcriptional activator Hnf-6 is coexpressed with its target gene Hnf-3-β in the developing murine liver and pancreas. Dev Biol 192: 228–246
Reddy JK, Rao MS, Yeldandi AV, Tan XD, Dwivedi RS (1991) Pancreatic hepatocytes. An in vivo model for cell lineage in pancreas of adult rat. Dig Dis Sci 36: 502–509
Resnick JL, Bixler LS, Cheng L, Donovan PJ (1992) Long-term proliferation of mouse primordial germ cells in culture. Nature 359: 550–551
Reubinoff B, Pera M, Fong C, Trounson A, Bongso A (2000) Embryonic stem cell lines from human blastocysts: Somatic differentiation in vitro. Nature Biotech 18: 399–404
Ritz-Laser B, Estreicher A, Klages N, Saule S, Philippe J (1999) Pax-6 and Cdx-2/3 interact to activate glucagon gene expression on the G(1) control element. J Biol Chem 274: 4124–4132
Ritz-Laser B, Estreicher A, Gauthier B, Philippe J (2000) The paired homeodomain transcription factor Pax-2 is expressed in the endocrine pancreas and transactivates the glucagon gene promoter. J Biol Chem 275: 32708–32715
Ritz-Laser B, Estreicher A, Gauthier BR, Mamin A, Edlund H, Philippe J (2002) The pancreatic β-cell-specific transcription factor Pax-4 inhibits glucagon gene expression through Pax-6. Diabetologia 45: 97–107
Ritz-Laser B et al. (2003) Ectopic expression of the β-cell specific transcription factor Pdx1 inhibits glucagon gene transcription. Diabetologia 46: 810–821
Rosenberg L (1995) In vivo cell transformation: Neogenesis of β-cells from pancreatic ductal cells. Cell Transpl 4: 371–383
Rosenberg L, Brown RA, Duguid WP (1983) A new approach to the induction of duct epithelial hyperplasia and nesidioblastosis by cellophane wrapping of the hamster pancreas. J Surg Res 35: 63–72
Rosenberg L, Duguid WP, Vinik AI (1989) The effect of cellophane wrapping of the pancreas in the Syrian golden hamster: Autoradiographic observations. Pancreas 4: 31–37
Rossi JM, Dunn NR, Hogan BLM, Zaret KS (1998) Distinct mesodermal signals, including BMPs from the septum transversum mesenchyme, are required in combination for hepatogenesis from the endoderm. Genes Dev 15: 1998–2009
Rouiller DG, Cirrulli V, Halban P (1991) Uvomorulin mediates calcium-dependent aggregation of islet cells, whereas calcium-independent cell adhesion molecules distinguish between islet cells types. Dev Biol 148: 233–242
Ryan E et al. (2001) Clinical outcomes and insulin secretion after islet transplantation with the Edmonton protocol. Diabetes 50: 710–719
Ryan EA, Lakey JRT, Paty BW et al. (2002) Successful islet transplantation — Continued insulin reserve provides long-term glycemic control. Diabetes 51: 2148–2157
Sander M, Neubüser A, Kalamaras J, Ee H, Martin G, German M (1997) Genetic analysis reveals that Pax6 is required for normal transcription of pancreatic hormone genes and islet development. Genes Dev 11: 1662–1673
Sander M, Sussel L, Conners J et al. (2000) Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of β-cell formation in the pancreas. Development 127: 5533–5540
Scearce LM et al. (2002) Functional genomics of the endocrine pancreas — The pancreas clone set and PancChip, new resources for diabetes research. Diabetes 51: 1997–2004
Schwitzgebel V, Scheel D, Conners J et al. (2000) Expression of neurogenin3 reveals an islet cell precursor population in the pancreas. Development 127: 3533–3542
Selander L, Edlund H (2002) Nestin is expressed in mesenchymal and not epithelial cells of the developing mouse pancreas. Mech Dev 113: 189–192
Serup P, Petersen HP, Petersen EE et al. (1995) The homeo-domain protein IPF-1/STF-1 is expressed in a subset of islet cells and promotes rat insulin 1 gene expression dependent on an intact El helix-loop-helix factor binding site. Biochem J 310: 997–1003
Shamblott M, Axelman J, Wang S et al. (1998) Derivation of pluripotent stem cells from cultured human primordial germ cells. Proc Natl Acad Sci USA 95: 13726–13731
Shapiro A, Lakey J, Ryan E, Korbutt G, Toth E, Warnock G, Kneteman N, RV R (2000) Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Eng J Med 343: 230–238
Shih DQ, Screenan S, Munoz KN et al. (2001) Loss of HNF-1α function in mice leads to abnormal expression of genes involved in pancreatic islet development and metabolism. Diabetes 50: 2472–2480
Shih DQ, Heimesaat M, Kuwajima S, Stein R, Wright CV, Stoffel M (2002) Profound defects in pancreatic β-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-lα, and Hnf-3β. Proc Natl Acad Sci USA 99: 3818–3823
Shimajiri Y, Sanke T, Furuta H et al. (2000) A missense mutation of the Pax4 gene in Japanese type 2 diabetic subjects. Diabetes 49: A202
Shimajiri Y, Sanke T, Furuta H et al. (2001) A missense mutation of Pax4 gene (R121W) is associated with type 2 diabetes in Japanese. Diabetes 50: 2864–2869
Smith SB, Gasa R, Watada H, Wang JH, Griffen SC, German MS (2003) Neurogenin3 and hepatic nuclear factor 1 cooperate in activating pancreatic expression of Pax4. J Biol Chem 278: 38254–38259
Song SY et al. (1999) Expansion of Pdx1-expressing pancreatic epithelium and islet neogenesis in transgenic mice overexpressing transforming growth factor α. Gastroenterology 117: 1416–1426
Soria B, Roche E, Berna G, Leon-Quinto T, Reig J, Martin F (2000) Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes 49: 157–162
Soria B, Skoudy A, Martin F (2001) From stem cells to β cells: New strategies in cell therapy of diabetes mellitus. Diabetologia 44: 407–415
Sosa-Pineda B, Chowdhury K, Torres M, Oliver G, Gruss P (1997) The Pax4 gene is essential for differentiation of insulin-producing β-cells in the mammalian pancreas. Nature 386: 399–402
Sreenan SK et al. (1998) Adaptation to hyperglycemia enhances insulin secretion in glucokinase mutant mice. Diabetes 47: 1881–1888
Stefan Y, Meda P, Neufeld M, Orci L (1987) Stimulation of insulin secretion reveals heterogeneity of pancreatic B cells in vivo. J Clin Invest 80: 175–183
Stewart CL, Gadi I, Bhatt H (1994) Stem cells from primordial germ cells can reenter the germ line. Dev Biol 161: 626–628
Staffers D, Zinkin N, Stanojevic V, Clarke W, Habener J (1997) Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. Nature Genet 15: 106–110
Staffers D, Ferrer J, Clarke W, Habener J (1998 a) Early-onset type-II diabetes mellitus (M0DY4) linked to IPF1. Nature Genet 17: 138–139
Staffers DA, Stanojevic V, Habener JF (1998b) Insulin promoter factor-1 gene mutation linked to early-onset type 2 diabetes mellitus directs expression of a dominant negative isoprotein. J Clin Invest 102: 232–241
St-Onge L, Sosa-Pineda B, Chowdhury K, Mansouri A, Gruss P (1997) Pax6 is required for differentiation of glucagon-producing α-cells in mouse pancreas. Nature 387: 406–409
St-Onge L, Wehr R, Gruss P (1999) Pancreas development and diabetes. Curr Opin Genet Dev 9: 295–300
Streuli C (1999) Extracellular matrix remodelling and cellular differentiation. Curr Opin Cell Biol 11: 634–640
Sussel L, Kalamaras J, Hartigan-O’Connor D, Meneses J, Pedersen R, Rubenstein J, German M (1998) Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to arrested differentiation of pancreatic β-cells. Development 125: 2213–2221
Suszko MI, Lo DJ, Suh H, Camper SA, Woodruff TK (2003) Regulation of the rat follicle-stimulating hormone beta-subunit promoter by activin. Mol Endocrinol 17: 318–332
Suzuki A, Zheng YW et al. (2002) Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver. J Cell Biol 156: 173–184
Swift GH, Liu Y, Rose SD et al. (1998) An endocrine-exocrine switch in the activity of the pancreatic homeodo-main protein Pdx1 through formation of a trimeric complex with Pbx1b and Mrg1 (Meis2). Mol Cell Biol 18: 5109–5120
Teitelman G, Alpert S, Polack JM, Martinez A, Hanahan D (1993) Precursor cells of mouse endocrine pancreas co-express insulin, glucagon and the neuronal protein tyrosine hydroxylase and neuropeptide Y, but not pancreatic polypeptide. Development 118: 1031–1039
Thayer SP et al. (2003) Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature 425: 851–856
Thomas H et al. (2001) A distant upstream promoter of the HNF-4α gene connects the transcription factors involved in maturity-onset diabetes of the young. Hum Mol Gen 10: 2089–2097
Thomson J, Itskovitz-Eldor J, Shapiro S, Waknitz M, Swiergiel J, Marshall V, Jones J (1998) Embryonic stem cell lines derived from human blastocysts. Science 282: 1145–1147
Thor S, Ericson J, Brännström T, Edlund T (1991) The homeodomain LIM protein Isl-1 is expressed in subsets of neurons and endocrine cells in the adult rat. Neuron 7: 881–889
Trimble ER, Halban PA, Wollheim CB, Renold AE (1982) Functional differences between rat islets of ventral and dorsal pancreatic origin. J Clin Invest 69: 405–413
Ueda Y (2000) Activin A increases Pax4 gene expression in pancreatic β cell lines. FEBS Lett 480: 101–105
Vaxillaire M et al. (1995) A gene for maturity onset diabetes of the young (MODY) maps to chromosome 12q. Nat Genet 9: 418–423
Velho G, Petersen KF, Perseghin G et al. (1996) Impaired hepatic glycogen synthesis in glucokinase-deficient (MODY-2) subjects. J Clin Invest 98: 1755–1761
Vu TH, Werb Z (2000) Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev 14: 2123–2133
Waguri M et al. (1997) Demonstration of two different processes of β-cell regeneration in a new diabetic mouse model induced by selective perfusion of alloxan. Diabetes 46: 1281–1290
Wang RN, Kloppel G, Bouwens L (1995) Duct-to islet-cell differentiation and islet growth in the pancreas of duct-ligated adult rats. Diabetologia 38: 1405–1411
Weinstein DC, Ruiz i Altaba A et al. (1994) The winged-helix transcription factor HNF-3β is required for notochord development in the mouse embryo. Cell 78: 575–588
Weir GC, Bonner-Weir S (1997) Scientific and political impediments to successful islet transplantation. Diabetes 46: 1247–1256
Winter WE, Silverstein JH (2000) Molecular and genetic bases for maturity onset diabetes of youth. Curr Opin Pediatr 12: 388–393
Wobus AM (2001) Potential of embryonic stem cells. Mol Aspects Med 22: 149–164
Wobus AM, Holzhausen H, Jakel P, Schoneich J (1984) Characterization of a pluripotent stem cell line derived from a mouse embryo. Exp Cell Res 152: 212–219
Wobus AM, Guan K, Pich U (2001) In vitro differentiation of embryonic stem cells and analysis of cellular phenotypes. Methods Mol Biol 158: 263–286
Wu H, Macfarlane WM, Tadayyon M, Arch JRS, James RFL, Docherty K (1999) Insulin stimulates pancreatic-duodenal homoeobox factor-1 (PDX1) DNA-binding activity and insulin promoter activity in pancreatic β cells. Biochem J 344: 813–818
Wu KL et al. (1997) Hepatocyte nuclear factor 3β is involved in pancreatic β-cell-specific transcription of the Pdx-1 gene. Mol Cell Biol 17: 6002–6013
Yamagata K et al. (1996 a) Mutations in the hepatocyte nuclear factor-4α gene in maturity-onset diabetes of the young (M0DY1). Nature 384: 458–460
Yamagata K et al. (1996 b) Mutations in the hepatocyte nuclear factor-1α gene in maturity-onset diabetes of the young (M0DY3). Nature 384: 455–458
Yamaoka T et al. (1998) Hypoplasia of pancreatic islets in transgenic mice expressing activin receptor mutants. J Clin Invest 102: 294–301
Yamaoka T, Yano M, Yamada T et al. (2000) Diabetes and pancreatic tumours in transgenic mice expressing Pax 6. Diabetologia 43: 332–339
Yang LJ, Li SW, Hatch H, Ahrens K, Cornelius JG, Petersen BE, Peck AB (2002) In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells. Proc Natl Acad Sci USA 99: 8078–8083
Ying LT, Li L, Westphal H, Chin C (1998) Sonic hedgehog is essential to foregut development. Nature Genet 20: 58–61
Zalzman M, Gupta S, Giri RK et al. (2003) Reversal of hyperglycemia in mice by using human expandable insulin-producing cells differentiated from fetal liver progenitor cells. Proc Natl Acad Sci USA 100: 7253–7258
Zhang Y, Mashima H, Kojima I (2001) Changes in the expression of transcription factors in pancreatic AR42 J cells during differentiation into insulin-producing cells. Diabetes 50: S10–S14
Zulewski H, Abraham EJ, Gerlach MJ et al. (2001) Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes 50: 521–533
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St-Onge, L., Wagner, M. (2006). Regulation der Entwicklung des Pankreas. In: Ganten, D., Ruckpaul, K., Köhrle, J. (eds) Molekularmedizinische Grundlagen von para- und autokrinen Regulationsstörungen. Molekulare Medizin. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-28782-5_2
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