PDX-1

Summary

Gene Symbol: PDX-1
Description: pancreatic and duodenal homeobox 1
Alias: GSF, IDX-1, IPF1, IUF1, MODY4, PAGEN1, PDX-1, STF-1, pancreas/duodenum homeobox protein 1, IPF-1, IUF-1, glucose-sensitive factor, insulin promoter factor 1, homeodomain transcription factor, insulin upstream factor 1, islet/duodenum homeobox-1, pancreatic-duodenal homeobox factor 1, somatostatin transcription factor 1, somatostatin-transactivating factor 1
Species: human
Products:     PDX-1

Top Publications

  1. Elbein S, Karim M. Does the aspartic acid to asparagine substitution at position 76 in the pancreas duodenum homeobox gene (PDX1) cause late-onset type 2 diabetes?. Diabetes Care. 2004;27:1968-73 pubmed
  2. Macfarlane W, Frayling T, Ellard S, Evans J, Allen L, Bulman M, et al. Missense mutations in the insulin promoter factor-1 gene predispose to type 2 diabetes. J Clin Invest. 1999;104:R33-9 pubmed
    ..We conclude that mutations in the IPF-1 gene may predispose to type 2 diabetes and are a rare cause of MODY and pancreatic agenesis, with the phenotype depending upon the severity of the mutation. ..
  3. Glick E, Leshkowitz D, Walker M. Transcription factor BETA2 acts cooperatively with E2A and PDX1 to activate the insulin gene promoter. J Biol Chem. 2000;275:2199-204 pubmed
  4. Feanny M, Fagan S, Ballian N, Liu S, Li Z, Wang X, et al. PDX-1 expression is associated with islet proliferation in vitro and in vivo. J Surg Res. 2008;144:8-16 pubmed
    ..The increase was seen in the first 24 h. These findings suggest a possible relationship between PDX-1 and the state of islet proliferation, islet-to-ductal transdifferentiation, apoptosis, and the expression of SSTRs. ..
  5. Cockburn B, Bermano G, Boodram L, Teelucksingh S, Tsuchiya T, Mahabir D, et al. Insulin promoter factor-1 mutations and diabetes in Trinidad: identification of a novel diabetes-associated mutation (E224K) in an Indo-Trinidadian family. J Clin Endocrinol Metab. 2004;89:971-8 pubmed
    ..of age and a family history of diabetes for mutations in the minimal promoter and coding region of the IPF-1 gene (IPF1)...
  6. Nicolino M, Claiborn K, Senée V, Boland A, Stoffers D, Julier C. A novel hypomorphic PDX1 mutation responsible for permanent neonatal diabetes with subclinical exocrine deficiency. Diabetes. 2010;59:733-40 pubmed publisher
    ..We found a novel mutation in the pancreatic and duodenal homeobox 1 gene (PDX1, IPF1) in the two patients, which segregated with diabetes in the homozygous state...
  7. Samaras S, Cissell M, Gerrish K, Wright C, Gannon M, Stein R. Conserved sequences in a tissue-specific regulatory region of the pdx-1 gene mediate transcription in Pancreatic beta cells: role for hepatocyte nuclear factor 3 beta and Pax6. Mol Cell Biol. 2002;22:4702-13 pubmed
    ..Collectively, these data suggest an important role for both HNF3 beta and Pax6 in regulating pdx-1 expression in beta cells. ..
  8. Stoffers D, Zinkin N, Stanojevic V, Clarke W, Habener J. Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. Nat Genet. 1997;15:106-10 pubmed
    The homeodomain protein IPF1 (also known as IDX1, STF1 and PDX1; see Methods) is critical for development of the pancreas in mice and is a key factor for the regulation of the insulin gene in the beta-cells of the endocrine pancreas...
  9. Hani E, Stoffers D, Chevre J, Durand E, Stanojevic V, Dina C, 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 pubmed
    ..We propose that IPF-1 mutations can cause MODY or apparently monogenic late-onset diabetes and that they represent a significant risk factor for type 2 diabetes in humans. ..

More Information

Publications98

  1. 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 pubmed
    ..These data demonstrate that the murine GLUT2 promoter is controlled by the PDX-1 homeobox factor through the identified GLUT2TAAT motif. ..
  2. Hui H, Perfetti R. Pancreas duodenum homeobox-1 regulates pancreas development during embryogenesis and islet cell function in adulthood. Eur J Endocrinol. 2002;146:129-41 pubmed
    ..The dual action of PDX-1, as a differentiation factor during embryogenesis and as a regulator of islet cell physiology in mature islet cells, underscores the unique role of PDX-1 in health and disease of the human endocrine pancreas. ..
  3. Zhou J, Pineyro M, Wang X, Doyle M, Egan J. Exendin-4 differentiation of a human pancreatic duct cell line into endocrine cells: involvement of PDX-1 and HNF3beta transcription factors. J Cell Physiol. 2002;192:304-14 pubmed
    ..Our results indicate that EX-4 activates adenylyl cyclase and MAP kinase which, in turn, may lead to activation of transcription factors necessary for an endocrine phenotype. ..
  4. Haaland W, Scaduto D, Maldonado M, Mansouri D, Nalini R, Iyer D, et al. A-beta-subtype of ketosis-prone diabetes is not predominantly a monogenic diabetic syndrome. Diabetes Care. 2009;32:873-7 pubmed publisher
    ..Several A-beta- KPD patients have low-frequency variants in HNF1A, PDX1, or PAX4 genes, which may be of functional significance in their pathophysiology. ..
  5. Gragnoli C, Stanojevic V, Gorini A, Von Preussenthal G, Thomas M, Habener J. IPF-1/MODY4 gene missense mutation in an Italian family with type 2 and gestational diabetes. Metabolism. 2005;54:983-8 pubmed
    ..Genetic variation in insulin promoter factor-1 (IPF1) (MODY4) is uncommon but may contribute to early- or late-onset diabetes as part of a polygenic background...
  6. Aviv V, Meivar Levy I, Rachmut I, Rubinek T, Mor E, Ferber S. Exendin-4 promotes liver cell proliferation and enhances the PDX-1-induced liver to pancreas transdifferentiation process. J Biol Chem. 2009;284:33509-20 pubmed publisher
    ..Understanding the cellular and molecular basis of the transdifferentiation process will allow us to increase the efficiency of the reprogramming process and optimize its therapeutic merit. ..
  7. Li Y, Zhang R, Qiao H, Zhang H, Wang Y, Yuan H, et al. Generation of insulin-producing cells from PDX-1 gene-modified human mesenchymal stem cells. J Cell Physiol. 2007;211:36-44 pubmed
    ..These findings validate the hMSCs model system as a potential basis for enrichment of human beta cells or their precursors, and a possible source for cell replacement therapy in diabetes. ..
  8. Weng J, Macfarlane W, Lehto M, Gu H, Shepherd L, Ivarsson S, et al. Functional consequences of mutations in the MODY4 gene (IPF1) and coexistence with MODY3 mutations. Diabetologia. 2001;44:249-58 pubmed
    The aim of this study was to examine the putative role of mutations in the insulin promoter 1 (IPF1) gene in early-onset diabetes...
  9. Schwitzgebel V, Mamin A, Brun T, Ritz Laser B, Zaiko M, Maret A, et al. Agenesis of human pancreas due to decreased half-life of insulin promoter factor 1. J Clin Endocrinol Metab. 2003;88:4398-406 pubmed
    ..Normal pancreas development is controlled by a cascade of transcription factors, where insulin promoter factor 1 (IPF1) plays a crucial role. Here, we describe two novel mutations in the IPF1 gene leading to pancreas agenesis...
  10. Khoo C, Yang J, Weinrott S, Kaestner K, Naji A, Schug J, et al. Research resource: the pdx1 cistrome of pancreatic islets. Mol Endocrinol. 2012;26:521-33 pubmed publisher
  11. Le Lay J, Matsuoka T, Henderson E, Stein R. Identification of a novel PDX-1 binding site in the human insulin gene enhancer. J Biol Chem. 2004;279:22228-35 pubmed
    ..These results demonstrate that the GG2 element, despite its divergence from the core homeodomain consensus binding motif, is a site for PDX-1 activation in the human insulin gene. ..
  12. Liu S, Ballian N, Belaguli N, Patel S, Li M, Templeton N, et al. PDX-1 acts as a potential molecular target for treatment of human pancreatic cancer. Pancreas. 2008;37:210-20 pubmed publisher
    ..Down-regulation of PDX-1 expression inhibits pancreatic cancer cell growth in vitro and in vivo, implying its use as a potential therapeutic target for the treatment of pancreatic cancer. ..
  13. Watada H, Kajimoto Y, Kaneto H, Matsuoka T, Fujitani Y, Miyazaki J, 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 pubmed
    ..the gene's expression to pancreatic beta-cells, bound by a homeodomain-containing transcription factor, PDX-1/IPF1/STF-1/IDX-1...
  14. Frandsen U, Porneki A, Floridon C, Abdallah B, Kassem M. Activin B mediated induction of Pdx1 in human embryonic stem cell derived embryoid bodies. Biochem Biophys Res Commun. 2007;362:568-74 pubmed
    ..The data suggest that additional suppression of Shh signaling may be required to allow for proper specification of pancreatic cell lineages in hESCs. ..
  15. Aramata S, Han S, Yasuda K, Kataoka K. Synergistic activation of the insulin gene promoter by the beta-cell enriched transcription factors MafA, Beta2, and Pdx1. Biochim Biophys Acta. 2005;1730:41-6 pubmed
    ..These results suggest that co-expression and functional synergism of these beta-cell enriched transactivators, MafA, Pdx1, and Beta2, are critical for establishing the beta-cell-specific and efficient expression of the insulin gene. ..
  16. Koizumi M, Doi R, Toyoda E, Masui T, Tulachan S, Kawaguchi Y, et al. Increased PDX-1 expression is associated with outcome in patients with pancreatic cancer. Surgery. 2003;134:260-6 pubmed
    ..Re-expression of PDX-1 may represent a return to a more de-differentiated state by more aggressive pancreatic cancers and may also represent an important new tumor marker for these aggressive cancers. ..
  17. Carty M, Lillquist J, Peshavaria M, Stein R, Soeller W. Identification of cis- and trans-active factors regulating human islet amyloid polypeptide gene expression in pancreatic beta-cells. J Biol Chem. 1997;272:11986-93 pubmed
    ..Since PDX-1 is highly enriched in beta and delta cells, these results suggest that this factor plays a principal role in defining islet beta cell- and delta cell-specific expression of the IAPP gene. ..
  18. Chen G, Yang X, Yang X, Li L, Luo J, Dong H, et al. Jia-Wei-Jiao-Tai-Wan ameliorates type 2 diabetes by improving ? cell function and reducing insulin resistance in diabetic rats. BMC Complement Altern Med. 2017;17:507 pubmed publisher
    ..This study suggests that JWJTW can ameliorate type 2 diabetes by improving ? cell function and reducing insulin resistance in diabetic rats. ..
  19. Xie Y, Zhu S, Zhong M, Yang M, Sun X, Liu J, et al. Inhibition of Aurora Kinase A Induces Necroptosis in Pancreatic Carcinoma. Gastroenterology. 2017;153:1429-1443.e5 pubmed publisher
    ..CCT137690 slowed growth of orthotopic tumors from PDAC cells in mice, and expression of AURKA and GSK3β associate with patient survival times. AURKA might be targeted for treatment of pancreatic cancer. ..
  20. Gundala N, Naidu V, Das U. Arachidonic acid and lipoxinA4 attenuate streptozotocin-induced cytotoxicity to RIN5 F cells in vitro and type 1 and type 2 diabetes mellitus in vivo. Nutrition. 2017;35:61-80 pubmed publisher
    ..AA is beneficial against STZ-induced cytotoxicity and T1- and T2DM by enhancing the production of LXA4. ..
  21. Yin X, Liu H, Zhang Y. Mulberry branch bark powder significantly improves hyperglycemia and regulates insulin secretion in type II diabetic mice. Food Nutr Res. 2017;61:1368847 pubmed publisher
    ..Thus, oral administration of MBBP regulated insulin secretion and effectively maintained normal levels of glucose metabolism in mice, which may be done by improving the antioxidant capacity and activating insulin signaling with T2D....
  22. Nimmakayala R, Seshacharyulu P, Lakshmanan I, Rachagani S, Chugh S, Karmakar S, et al. Cigarette Smoke Induces Stem Cell Features of Pancreatic Cancer Cells via PAF1. Gastroenterology. 2018;155:892-908.e6 pubmed publisher
    ..Levels of PAF1 are increased in pancreatic tumors of humans and mice with chronic cigarette smoke exposure. ..
  23. Gundala N, Naidu V, Das U. Arachidonic acid and lipoxin A4 attenuate alloxan-induced cytotoxicity to RIN5F cells in vitro and type 1 diabetes mellitus in vivo. Biofactors. 2017;43:251-271 pubmed publisher
    ..AA seems to bring about its beneficial actions against alloxan-induced cytotoxicity and type 1 DM by enhancing the production of LXA4. © 2016 BioFactors, 43(2):251-271, 2017. ..
  24. Annicotte J, Fayard E, Swift G, Selander L, Edlund H, Tanaka T, et al. Pancreatic-duodenal homeobox 1 regulates expression of liver receptor homolog 1 during pancreas development. Mol Cell Biol. 2003;23:6713-24 pubmed
    ..Taken together, our data indicate that PDX-1 controls LRH-1 expression and identify LRH-1 as a novel downstream target in the PDX-1 regulatory cascade governing pancreatic development, differentiation, and function. ..
  25. Kim D, Song L, Wang J, Wu H, Gu G, Sugi Y, et al. GRP94 Is an Essential Regulator of Pancreatic β-Cell Development, Mass, and Function in Male Mice. Endocrinology. 2018;159:1062-1073 pubmed publisher
    ..In aggregate, these findings indicate that GRP94 is an essential regulator of pancreatic β-cell development, mass, and function. ..
  26. Muniappan L, Ozcan S. Induction of insulin secretion in engineered liver cells by nitric oxide. BMC Physiol. 2007;7:11 pubmed
    ..Liver cells can be engineered to produce insulin and insulin secretion can be induced by treatment with L-arginine via the production of nitric oxide. ..
  27. Sha Y, Zhang Y, Cao J, Qian K, Niu B, Chen Q. Loureirin B promotes insulin secretion through inhibition of KATP channel and influx of intracellular calcium. J Cell Biochem. 2018;119:2012-2021 pubmed publisher
  28. Johannesson M, Ståhlberg A, Ameri J, Sand F, Norrman K, Semb H. FGF4 and retinoic acid direct differentiation of hESCs into PDX1-expressing foregut endoderm in a time- and concentration-dependent manner. PLoS ONE. 2009;4:e4794 pubmed publisher
    ..RA signaling mediated by the early induction of RARbeta through AA/Wnt3a is required for PDX1 expression. Part of RA's activity is mediated by FGF signaling. ..
  29. Kaitsuka T, Tomizawa K. Cell-Penetrating Peptide as a Means of Directing the Differentiation of Induced-Pluripotent Stem Cells. Int J Mol Sci. 2015;16:26667-76 pubmed publisher
    ..Here, we discuss the possibility of using CPPs as a means of directing the differentiation of iPS cells and other stem cell technologies. ..
  30. Cheng C, Villani V, Buono R, Wei M, Kumar S, Yilmaz O, et al. Fasting-Mimicking Diet Promotes Ngn3-Driven ?-Cell Regeneration to Reverse Diabetes. Cell. 2017;168:775-788.e12 pubmed publisher
    ..These results indicate that a FMD promotes the reprogramming of pancreatic cells to restore insulin generation in islets from T1D patients and reverse both T1D and T2D phenotypes in mouse models. PAPERCLIP. ..
  31. Qadir M, Álvarez Cubela S, Klein D, Lanzoni G, García Santana C, Montalvo A, et al. P2RY1/ALK3-Expressing Cells within the Adult Human Exocrine Pancreas Are BMP-7 Expandable and Exhibit Progenitor-like Characteristics. Cell Rep. 2018;22:2408-2420 pubmed publisher
    ..Our studies confirm the existence of progenitor cells in the adult human pancreas and suggest a specific anatomical location within the ductal and glandular networks. ..
  32. Cai J, Yu C, Liu Y, Chen S, Guo Y, Yong J, et al. Generation of homogeneous PDX1(+) pancreatic progenitors from human ES cell-derived endoderm cells. J Mol Cell Biol. 2010;2:50-60 pubmed publisher
    ..Thus, we present a highly efficient and reproducible protocol for generating PDX1(+) pancreatic progenitor cells from hES cells. ..
  33. Elbein S, Wang X, Karim M, Freedman B, Bowden D, Shuldiner A, et al. Role of a proline insertion in the insulin promoter factor 1 (IPF1) gene in African Americans with type 2 diabetes. Diabetes. 2006;55:2909-14 pubmed
    ..We identified an inframe insertion of a proline in the insulin promoter factor 1 (IPF1) gene (InsCCG243), which was relatively common (minor allele frequency approximately 0...
  34. Wu J, Liu X, Nayak S, Pitarresi J, Cuitino M, Yu L, et al. Generation of a pancreatic cancer model using a Pdx1-Flp recombinase knock-in allele. PLoS ONE. 2017;12:e0184984 pubmed publisher
    ..This will provide an excellent in vivo tool to study the roles of genes in different cell types and multiple cell compartments within the pancreatic tumor microenvironment. ..
  35. Fodor A, Harel C, Fodor L, Armoni M, Salmon P, Trono D, et al. Adult rat liver cells transdifferentiated with lentiviral IPF1 vectors reverse diabetes in mice: an ex vivo gene therapy approach. Diabetologia. 2007;50:121-30 pubmed
    ..pancreatic duodenal homeobox 1 (PDX1, now known as insulin promoter factor 1, homeodomain transcription factor [IPF1])...
  36. Lebrun P, Montminy M, Van Obberghen E. Regulation of the pancreatic duodenal homeobox-1 protein by DNA-dependent protein kinase. J Biol Chem. 2005;280:38203-10 pubmed
    ..e. glut2 and glucokinase. Our study demonstrates that radiation, through the activation of DNA-PK, may regulate PDX-1 protein expression. ..
  37. Villamayor L, Rodríguez Seguel E, Araujo R, Carrasco M, Bru Tari E, Mellado Gil J, et al. GATA6 Controls Insulin Biosynthesis and Secretion in Adult ?-Cells. Diabetes. 2018;67:448-460 pubmed publisher
    ..These findings demonstrate the essential role of GATA6 in ?-cell function. ..
  38. Gefen Halevi S, Rachmut I, Molakandov K, Berneman D, Mor E, Meivar Levy I, et al. NKX6.1 promotes PDX-1-induced liver to pancreatic ?-cells reprogramming. Cell Reprogram. 2010;12:655-64 pubmed publisher
    ..The individual and concerted effects of pancreatic transcription factors in adult extra-pancreatic cells, is expected to facilitate developing regenerative medicine approaches for cell replacement therapy in diabetics. ..
  39. Keller M, Gatti D, Schueler K, Rabaglia M, Stapleton D, Simecek P, et al. Genetic Drivers of Pancreatic Islet Function. Genetics. 2018;209:335-356 pubmed publisher
  40. Galivo F, Benedetti E, Wang Y, Pelz C, Schug J, Kaestner K, et al. Reprogramming human gallbladder cells into insulin-producing ?-like cells. PLoS ONE. 2017;12:e0181812 pubmed publisher
  41. Seeberger K, Anderson S, Ellis C, Yeung T, Korbutt G. Identification and differentiation of PDX1 ?-cell progenitors within the human pancreatic epithelium. World J Diabetes. 2014;5:59-68 pubmed publisher
    ..05). PDX1(+) cells were confined to adherent epithelial cell aggregates and not vimentin(+) cells (mesenchymal), suggesting that EMT is not a mechanism for generating pancreatic progenitor cells. ..
  42. Ida S, Morino K, Sekine O, Ohashi N, Kume S, Chano T, et al. Diverse metabolic effects of O-GlcNAcylation in the pancreas but limited effects in insulin-sensitive organs in mice. Diabetologia. 2017;60:1761-1769 pubmed publisher
    ..Our results provide novel insight into O-GlcNAc biology and physiology in glucose metabolism. ..
  43. Catenacci D, Junttila M, Karrison T, Bahary N, Horiba M, Nattam S, et al. Randomized Phase Ib/II Study of Gemcitabine Plus Placebo or Vismodegib, a Hedgehog Pathway Inhibitor, in Patients With Metastatic Pancreatic Cancer. J Clin Oncol. 2015;33:4284-92 pubmed publisher
    ..Our preclinical and clinical results revealed no statistically significant differences with respect to drug delivery or treatment efficacy using vismodegib. ..
  44. Xu J, Cui J, del Campo A, Shin C. Four and a Half LIM Domains 1b (Fhl1b) Is Essential for Regulating the Liver versus Pancreas Fate Decision and for β-Cell Regeneration. PLoS Genet. 2016;12:e1005831 pubmed publisher
    ..Altogether, these data reveal novel and critical functions of Fhl1b in the hepatic versus pancreatic fate decision and in β-cell regeneration. ..
  45. Nissim S, Weeks O, Talbot J, Hedgepeth J, Wucherpfennig J, Schatzman Bone S, et al. Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development. Dev Biol. 2016;418:108-123 pubmed publisher
    ..These findings define critical iterative and pleiotropic roles for Nr5a2 at distinct stages of pancreas and liver organogenesis, and provide novel perspectives for interpreting the role of Nr5a2 in disease. ..
  46. Karunakaran U, Moon J, Lee H, Won K. CD36 initiated signaling mediates ceramide-induced TXNIP expression in pancreatic beta-cells. Biochim Biophys Acta. 2015;1852:2414-22 pubmed publisher
    ..These data suggest that CD36 dependent NF-?B-TXNIP signaling contributes to the ceramide-induced pathogenesis of pancreatic ?-cell dysfunction and failure. ..
  47. Yang Z, Zhang Q, Lu Q, Jia Z, Chen P, Ma K, et al. ISL-1 promotes pancreatic islet cell proliferation by forming an ISL-1/Set7/9/PDX-1 complex. Cell Cycle. 2015;14:3820-9 pubmed publisher
    ..Furthermore, the formation of the ISL-1/Set7/9/PDX-1 complex is positively associated with insulin-like growth factor-1 treatment in NIT and HIT-T15 cells in vitro, while may be negatively correlated with age in vivo. ..
  48. Pondugala P, Sasikala M, Guduru V, Rebala P, Nageshwar Reddy D. Interferon-γ Decreases Nuclear Localization of Pdx-1 and Triggers β-Cell Dysfunction in Chronic Pancreatitis. J Interferon Cytokine Res. 2015;35:523-9 pubmed publisher
    ..Pretreatment with polyphenolic compound EGCG restored the nuclear localization of Pdx-1. These results suggest that IFN-γ induced β-cell dysfunction is mediated through decreased nuclear localization of Pdx-1. ..
  49. Kang R, Xie Y, Zhang Q, Hou W, Jiang Q, Zhu S, et al. Intracellular HMGB1 as a novel tumor suppressor of pancreatic cancer. Cell Res. 2017;27:916-932 pubmed publisher
    ..Diminished nuclear and total cellular expression of HMGB1 in PDAC patients correlates with poor overall survival, supporting intracellular HMGB1 as a novel tumor suppressor with prognostic and therapeutic relevance in PDAC. ..
  50. Chen N, Singh G, Koenig A, Liou G, Storz P, Zhang J, et al. NFATc1 Links EGFR Signaling to Induction of Sox9 Transcription and Acinar-Ductal Transdifferentiation in the Pancreas. Gastroenterology. 2015;148:1024-1034.e9 pubmed publisher
    ..Strategies designed to disrupt this pathway might be developed to prevent pancreatic cancer initiation in high-risk patients with chronic pancreatitis. ..
  51. Tummers W, Kimura R, Abou Elkacem L, Beinat C, Vahrmeijer A, Swijnenburg R, et al. Development and Preclinical Validation of a Cysteine Knottin Peptide Targeting Integrin αvβ6 for Near-infrared Fluorescent-guided Surgery in Pancreatic Cancer. Clin Cancer Res. 2018;24:1667-1676 pubmed publisher
    ..This agent can help improve the stratification of patients for a potentially curative, margin-negative resection. Clin Cancer Res; 24(7); 1667-76. ©2018 AACR. ..
  52. Srivastava A, Dadheech N, Vakani M, Gupta S. Swertisin ameliorates diabetes by triggering pancreatic progenitors for islet neogenesis in Streptozotocin treated BALB/c mice. Biomed Pharmacother. 2018;100:221-225 pubmed publisher
    ..Thus, this short study highlights pancreatic innate capability to regenerate and recover using its own resident progenitors upon appropriate stimulus, which could culminate into an effective diabetic therapy. ..
  53. Purohit A, Varney M, Rachagani S, Ouellette M, Batra S, Singh R. CXCR2 signaling regulates KRAS(G¹²D)-induced autocrine growth of pancreatic cancer. Oncotarget. 2016;7:7280-96 pubmed publisher
    ..Together, these data demonstrate the role of CXCR2 signaling in KRAS(G12D)-induced growth transformation and progression in PDAC. ..
  54. D Costa Z, Jones K, Azad A, van Stiphout R, Lim S, Gomes A, et al. Gemcitabine-Induced TIMP1 Attenuates Therapy Response and Promotes Tumor Growth and Liver Metastasis in Pancreatic Cancer. Cancer Res. 2017;77:5952-5962 pubmed publisher
    ..Overall, our results identify TIMP1 upregulation as a resistance mechanism to gemcitabine and provide a rationale for combining chemo/radiotherapy with TIMP1 inhibitors in PDAC. Cancer Res; 77(21); 5952-62. ©2017 AACR. ..
  55. Gragnoli C, Cronsell J. Meta-analysis of the IPF1 D76N polymorphism in a worldwide type 2 diabetes population. Minerva Med. 2007;98:163-6 pubmed
    Mutations in the IPF1 gene cause MODY4; IPF1 D76N is a polymorphism, which inhibits the insulin promoter and decreases insulin-secretion...
  56. Reis A, Ye W, Dubois Laforgue D, Bellanne Chantelot C, Timsit J, Velho G. Mutations in the insulin promoter factor-1 gene in late-onset type 2 diabetes mellitus. Eur J Endocrinol. 2000;143:511-3 pubmed
    ..These differences in prevalence might be related to differences in the clinical profile of patients, such as age of onset of diabetes and associated obesity, as well as a family history of diabetes. ..
  57. Zhang L, Chen W, Dai Y, Zhu Z, Liu Q. Detection of expressional changes induced by intrauterine growth restriction in the developing rat pancreas. Exp Biol Med (Maywood). 2016;241:1446-56 pubmed publisher
    ..In conclusion, our data support the hypothesis that IUGR influences the development of the rat pancreas. We also identified new pathways that appear to be programmed by IUGR. ..
  58. Odem J, Munzinger E, Violand S, Van Morlan A, Rife D, Bachrach B. An infant with combination gene mutations for Monogenic Diabetes of Youth (MODY) 2 and 4, presenting with Diabetes Mellitus Requiring Insulin (DMRI) at 8 months of age. Pediatr Diabetes. 2009;10:550-3 pubmed publisher
    ..MODY2 results from a mutation in the glucokinase gene (GCK), which decreases enzyme activity. MODY4 results from a mutation in the insulin promoter factor-1 (IPF-1) gene, a transcription factor which regulates the ..
  59. Ma J, Wang J, Zhang W, Zou B, Chen W, Lam C, et al. Promoter hypermethylation and histone hypoacetylation contribute to pancreatic-duodenal homeobox 1 silencing in gastric cancer. Carcinogenesis. 2010;31:1552-60 pubmed publisher
    ..05). ChIP assay showed F383 was also associated with low hypoacetylation level of the histones. Promoter hypermethylation and histone hypoacetylation contribute to PDX1 silencing in gastric cancer. ..
  60. Yamada Y, Kato K, Oguri M, Yoshida T, Yokoi K, Watanabe S, et al. Association of genetic variants with atherothrombotic cerebral infarction in Japanese individuals with metabolic syndrome. Int J Mol Med. 2008;21:801-8 pubmed
    ..revealed that the 2445G-->A (Ala54Thr) polymorphism (rs1799883) of FABP2, the -108/3G-->4G polymorphism of IPF1 (S82168), the A-->G (Thr94Ala) polymorphism (rs2241883) of FABP1, the G-->A (Asp2213Asn) polymorphism (..
  61. Matsuoka T, Kawashima S, Miyatsuka T, Sasaki S, Shimo N, Katakami N, et al. Mafa Enables Pdx1 to Effectively Convert Pancreatic Islet Progenitors and Committed Islet α-Cells Into β-Cells In Vivo. Diabetes. 2017;66:1293-1300 pubmed publisher
    ..These results provide valuable insight into the fundamental mechanisms influencing islet cell plasticity in vivo. ..
  62. Hermann G, Konukiewitz B, Schmitt A, Perren A, Kloppel G. Hormonally defined pancreatic and duodenal neuroendocrine tumors differ in their transcription factor signatures: expression of ISL1, PDX1, NGN3, and CDX2. Virchows Arch. 2011;459:147-54 pubmed publisher
    ..The observed TF signatures do not allow us to distinguish P-NETs from D-NETs. ..
  63. Kim Y, Kim S, Mellado Gil J, Yadav H, Neidermyer W, Kamaraju A, et al. RB regulates pancreas development by stabilizing Pdx1. EMBO J. 2011;30:1563-76 pubmed publisher
    ..These results demonstrate an unanticipated regulatory mechanism for pancreatic development and ?-cell function, which involves RB-mediated stabilization of the pancreas-specific transcription factor Pdx-1...
  64. Liu Y, MacDonald R, Swift G. DNA binding and transcriptional activation by a PDX1.PBX1b.MEIS2b trimer and cooperation with a pancreas-specific basic helix-loop-helix complex. J Biol Chem. 2001;276:17985-93 pubmed
    ..PBX1b.MEIS2b complex cooperates with the PTF1 basic helix-loop-helix complex to activate an ELA1 minienhancer in HeLa cells and that this cooperation requires all three homeoprotein subunits, including the PDX1 activation domain. ..
  65. Cao B, Li R, Tian H, Jia N, Hu X, Ma Y, et al. [Effect of Electroacupuncture at "Weiwanxiashu" (EX-B 3) on Islet Morphology and the Expression of Pancreatic Glucagon-like Peptide-1 Receptor in Type 2 Diabetes Rats]. Zhen Ci Yan Jiu. 2017;42:107-13 pubmed
    ..05). EA treatment at EX-B 3 can reduce blood glucose via regulating pancreas function, increasing pancreatic GLP-1 R expression, and partly restoring the morphology of pancreas. ..
  66. Vilarino M, Rashid S, Suchy F, McNabb B, van der Meulen T, Fine E, et al. CRISPR/Cas9 microinjection in oocytes disables pancreas development in sheep. Sci Rep. 2017;7:17472 pubmed publisher
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    ..Overall, the data presented herein suggest that TBX15 might be involved in the pathophysiology of placental diseases. ..
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  69. Weng J, Ekelund M, Lehto M, Li H, Ekberg G, Frid A, et al. Screening for MODY mutations, GAD antibodies, and type 1 diabetes--associated HLA genotypes in women with gestational diabetes mellitus. Diabetes Care. 2002;25:68-71 pubmed
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    ..Copyright © 2016 John Wiley & Sons, Ltd. ..
  71. Guo Q, Zhu M, Wang L, Fan X, Lu Y, Wang Z, et al. Combined transfection of the three transcriptional factors, PDX-1, NeuroD1, and MafA, causes differentiation of bone marrow mesenchymal stem cells into insulin-producing cells. Exp Diabetes Res. 2012;2012:672013 pubmed publisher
    ..These findings suggest major implications for cell replacement strategies in generation of surrogate ?-cells for the treatment of diabetes. ..
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    ..Thus, it is likely that alteration of such transcription factors explains, at least in part, the molecular mechanism for beta-cell glucose toxicity found in diabetes. ..
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    Griseofulvin (GSF) is a classic antifungal drug that has been in clinical use for over 50 years, but its polymorphism was recognized only recently via melt crystallization...
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    ..Protected regions encompass six putative binding sites for the transcription factor PDX-1, as well as proposed CDX, hepatocyte nuclear factor-4, and GATA-type sites...
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    ..The results suggest that SFH prevents the degeneration of pancreatic islets via increasing SOD while hyperglycemia is alleviated by maintaining beta cell mass in type 2 diabetes model mice. ..
  76. Csóka B, Törő G, Vindeirinho J, Varga Z, Koscsó B, Németh Z, et al. A2A adenosine receptors control pancreatic dysfunction in high-fat-diet-induced obesity. FASEB J. 2017;31:4985-4997 pubmed publisher
    ..H., Kókai, E., Antonioli, L., Suleiman, M., Marchetti, P., Cseri, K., Deák, Á., Virág, L., Pacher, P., Bai, P., Haskó, G. A2A adenosine receptors control pancreatic dysfunction in high-fat-diet-induced obesity. ..
  77. McKenna B, Guo M, Reynolds A, Hara M, Stein R. Dynamic recruitment of functionally distinct Swi/Snf chromatin remodeling complexes modulates Pdx1 activity in islet β cells. Cell Rep. 2015;10:2032-42 pubmed publisher
    ..We discuss how context-dependent recruitment of coregulatory complexes by Pdx1 could impact pancreas cell development and adult islet β cell activity. ..
  78. Vinogradova T, Sverdlov E. PDX1: A Unique Pancreatic Master Regulator Constantly Changes Its Functions during Embryonic Development and Progression of Pancreatic Cancer. Biochemistry (Mosc). 2017;82:887-893 pubmed publisher
    ..Hence, PDX1 belongs to the family of master regulators with multiple and often antagonistic functions. ..
  79. Kondratyeva L, Chernov I, Zinovyeva M, Kopantzev E, Sverdlov E. Expression of master regulatory genes of embryonic development in pancreatic tumors. Dokl Biochem Biophys. 2017;475:250-252 pubmed publisher
    ..A simultaneous suppression of expression of these master factors may be critical for the neoplastic transformation of pancreatic cells. ..
  80. Zhou G, Wang H, Liu S, Shahi K, Lin X, Wu J, et al. p38 MAP kinase interacts with and stabilizes pancreatic and duodenal homeobox-1. Curr Mol Med. 2013;13:377-86 pubmed
    ..Taken together, our studies indicated that p38 MAP kinase is a positive regulator of PDX-1 stability and that p38 exerts its stabilizing effect on PDX-1 through a phosphorylation-dependent inhibition of PDX-1 ubiquitination. ..
  81. Ritz Laser B, Gauthier B, Estreicher A, Mamin A, Brun T, Ris F, et al. Ectopic expression of the beta-cell specific transcription factor Pdx1 inhibits glucagon gene transcription. Diabetologia. 2003;46:810-21 pubmed
    ..Cell-specific expression of the glucagon gene can only occur when Pdx1 expression extinguishes from the early alpha cell precursor. ..
  82. Rafati R, Jalal R, Asoodeh A, Matin M. Association of rs12255372 (TCF7L2) and D76N (PDX-1) Polymorphisms with Type 2 Diabetes in a Population Living in Northeast Iran. Arch Iran Med. 2015;18:376-8 pubmed publisher
    ..93, 95% CI = 1.60-7.68, P = 0.002) were significantly associated with an increased risk of T2DM. The rs12255372 SNP of TCF7L2 and D76N of PDX-1 genes may confer susceptibility to T2DM in the population living in Mashhad. ..
  83. Bernardo A, Cho C, Mason S, Docherty H, Pedersen R, Vallier L, et al. Biphasic induction of Pdx1 in mouse and human embryonic stem cells can mimic development of pancreatic beta-cells. Stem Cells. 2009;27:341-51 pubmed publisher
    ..Collectively, we show that this method of in vitro differentiation provides a template for inducing and studying ES cell differentiation into insulin-secreting cells. ..
  84. Akiyama T, Shida T, Yoshitomi H, Takano S, Kagawa S, Shimizu H, et al. Expression of Sex Determining Region Y-Box 2 and Pancreatic and Duodenal Homeobox 1 in Pancreatic Neuroendocrine Tumors. Pancreas. 2016;45:522-7 pubmed publisher
    ..The expression patterns of SOX2 and Pdx1 highly correlated with prognosis of p-NETs. These expression patterns may represent the biological and pathophysiological difference of p-NETs and indicate the origin of tumor. ..
  85. Yamanaka T, Tashima K, Takahashi R, Takashima S, Goto T, Hirabayashi M, et al. Direct comparison of Cryotop® vitrification and Bicell® freezing on recovery of functional rat pancreatic islets. Cryobiology. 2016;73:376-382 pubmed publisher
    ..These results suggest that rat pancreatic islets can be cryopreserved by Cryotop® vitrification-warming rather than Bicell® freeze-thawing, without considerable loss of in vitro β-cell function. ..
  86. Wei J, Ding D, Wang T, Liu Q, Lin Y. MiR-338 controls BPA-triggered pancreatic islet insulin secretory dysfunction from compensation to decompensation by targeting Pdx-1. FASEB J. 2017;31:5184-5195 pubmed publisher
    ..Wei, J., Ding, D., Wang, T., Liu, Q., Lin, Y. MiR-338 controls BPA-triggered pancreatic islet insulin secretory dysfunction from compensation to decompensation by targeting Pdx-1. ..
  87. Socorro M, Criscimanna A, Riva P, Tandon M, Prasadan K, Guo P, et al. Identification of Newly Committed Pancreatic Cells in the Adult Mouse Pancreas. Sci Rep. 2017;7:17539 pubmed publisher
  88. Mishra P, Singh S, Joshua I, Tyagi S. Stem cells as a therapeutic target for diabetes. Front Biosci (Landmark Ed). 2010;15:461-77 pubmed
    ..In this review we discussed stem cells as a potential future therapeutic target for the treatment of diabetes and associated diseases. ..
  89. Hayes H, Zhang L, Becker T, Haldeman J, Stephens S, Arlotto M, et al. A Pdx-1-Regulated Soluble Factor Activates Rat and Human Islet Cell Proliferation. Mol Cell Biol. 2016;36:2918-2930 pubmed
    ..In sum, this study identifies a mechanism by which Pdx-1 induces a soluble factor that is sufficient to stimulate both rat and human islet cell proliferation. ..