Ins2

Summary

Gene Symbol: Ins2
Description: insulin II
Alias: AA986540, Ins-2, InsII, Mody, Mody4, proinsulin, insulin-2
Species: mouse

Top Publications

  1. ncbi A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57BL/6 (Akita) mutant mice
    M Yoshioka
    Department of Hygiene, Akita University School of Medicine, Japan
    Diabetes 46:887-94. 1997
  2. pmc Ghrelin cells replace insulin-producing beta cells in two mouse models of pancreas development
    Catherine L Prado
    Department of Pediatrics, Barbara Davis Center, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, USA
    Proc Natl Acad Sci U S A 101:2924-9. 2004
  3. ncbi Insulin-promoter-factor 1 is required for pancreas development in mice
    J Jonsson
    Department of Microbiology, University of Umea, Sweden
    Nature 371:606-9. 1994
  4. pmc Circulating sphingolipid biomarkers in models of type 1 diabetes
    Todd E Fox
    Department of Pharmacology, Penn State College of Medicine, Milton S Hershey Medical Center, Hershey, PA, USA
    J Lipid Res 52:509-17. 2011
  5. pmc The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth
    Tadahiro Kitamura
    Naomi Berrie Diabetes Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York, USA
    J Clin Invest 110:1839-47. 2002
  6. ncbi The simultaneous loss of Arx and Pax4 genes promotes a somatostatin-producing cell fate specification at the expense of the alpha- and beta-cell lineages in the mouse endocrine pancreas
    Patrick Collombat
    Max Planck Institute for Biophysical Chemistry, Department of Molecular Cell Biology, Am Fassberg, 37077 Gottingen, Germany
    Development 132:2969-80. 2005
  7. pmc Islet-1 regulates Arx transcription during pancreatic islet alpha-cell development
    Jingxuan Liu
    Department of Pathology and Laboratory Medicine, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 286:15352-60. 2011
  8. pmc Nkx6 transcription factors and Ptf1a function as antagonistic lineage determinants in multipotent pancreatic progenitors
    Ashleigh E Schaffer
    Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA
    Dev Cell 18:1022-9. 2010
  9. pmc SOX9 is required for maintenance of the pancreatic progenitor cell pool
    Philip A Seymour
    Department of Developmental and Cell Biology, University of California, Irvine, CA 92697 2300, USA
    Proc Natl Acad Sci U S A 104:1865-70. 2007
  10. pmc Lack of both bradykinin B1 and B2 receptors enhances nephropathy, neuropathy, and bone mineral loss in Akita diabetic mice
    Masao Kakoki
    Department of Pathology and Laboratory Medicine and Nutrition, University of North Carolina, Chapel Hill, NC 27599, USA
    Proc Natl Acad Sci U S A 107:10190-5. 2010

Scientific Experts

Detail Information

Publications147 found, 100 shown here

  1. ncbi A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57BL/6 (Akita) mutant mice
    M Yoshioka
    Department of Hygiene, Akita University School of Medicine, Japan
    Diabetes 46:887-94. 1997
    ..This locus, which we named Mody4, was mapped to chromosome 7 in a region 2-8 cM distal to D7Mit189 (logarithm of odds [LOD] score = 15.6 and 10.3).
  2. pmc Ghrelin cells replace insulin-producing beta cells in two mouse models of pancreas development
    Catherine L Prado
    Department of Pediatrics, Barbara Davis Center, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, USA
    Proc Natl Acad Sci U S A 101:2924-9. 2004
    ..2 and Pax4 are required to specify or maintain differentiation of the beta cell fate. This finding also suggests that there is a genetic component underlying the balance between insulin and ghrelin in regulating glucose metabolism...
  3. ncbi Insulin-promoter-factor 1 is required for pancreas development in mice
    J Jonsson
    Department of Microbiology, University of Umea, Sweden
    Nature 371:606-9. 1994
    ..These findings show that IPF1 is needed for the formation of the pancreas and suggest that it acts to determine the fate of common pancreatic precursor cells and/or to regulate their propagation...
  4. pmc Circulating sphingolipid biomarkers in models of type 1 diabetes
    Todd E Fox
    Department of Pharmacology, Penn State College of Medicine, Milton S Hershey Medical Center, Hershey, PA, USA
    J Lipid Res 52:509-17. 2011
    ..metabolites by LC-MS/MS from two animal models of type 1 diabetes (streptozotocin-induced diabetic rats and Ins2(Akita) diabetic mice) to identify putative therapeutic targets and biomarkers...
  5. pmc The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth
    Tadahiro Kitamura
    Naomi Berrie Diabetes Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York, USA
    J Clin Invest 110:1839-47. 2002
    ..We propose that insulin/IGFs regulate beta cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts...
  6. ncbi The simultaneous loss of Arx and Pax4 genes promotes a somatostatin-producing cell fate specification at the expense of the alpha- and beta-cell lineages in the mouse endocrine pancreas
    Patrick Collombat
    Max Planck Institute for Biophysical Chemistry, Department of Molecular Cell Biology, Am Fassberg, 37077 Gottingen, Germany
    Development 132:2969-80. 2005
    ..Finally, our data provide evidence that both Arx and Pax4 act as transcriptional repressors that control the expression level of one another, thereby mediating proper endocrine fate allocation...
  7. pmc Islet-1 regulates Arx transcription during pancreatic islet alpha-cell development
    Jingxuan Liu
    Department of Pathology and Laboratory Medicine, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 286:15352-60. 2011
    ..Isl-1 represents the first known activator of Arx transcription in α-cells, here established to be acting through the conserved Re1 and Re2 control domains...
  8. pmc Nkx6 transcription factors and Ptf1a function as antagonistic lineage determinants in multipotent pancreatic progenitors
    Ashleigh E Schaffer
    Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA
    Dev Cell 18:1022-9. 2010
    ..Thus, cross-antagonism between Nkx6 and Ptf1a in multipotent progenitors governs the equilibrium between endocrine and acinar cell neogenesis required for normal pancreas development...
  9. pmc SOX9 is required for maintenance of the pancreatic progenitor cell pool
    Philip A Seymour
    Department of Developmental and Cell Biology, University of California, Irvine, CA 92697 2300, USA
    Proc Natl Acad Sci U S A 104:1865-70. 2007
    ..These findings will be of major significance for the development of in vitro protocols for cell replacement therapies...
  10. pmc Lack of both bradykinin B1 and B2 receptors enhances nephropathy, neuropathy, and bone mineral loss in Akita diabetic mice
    Masao Kakoki
    Department of Pathology and Laboratory Medicine and Nutrition, University of North Carolina, Chapel Hill, NC 27599, USA
    Proc Natl Acad Sci U S A 107:10190-5. 2010
    ..nephropathy, neuropathy, and osteopathy in male mice heterozygous for the Akita diabetogenic mutation in the insulin 2 gene (Ins2)...
  11. ncbi Pancreas-specific deletion of beta-catenin reveals Wnt-dependent and Wnt-independent functions during development
    Jessica Dessimoz
    Swiss Institute for Experimental Cancer Research, Chemin des Boveresses 155, Case Postale, CH 1066 Epalinges s Lausanne, Switzerland
    Curr Biol 15:1677-83. 2005
    ..These effects are likely to be due to the function of beta-catenin at the membrane. Mice later recover from pancreatitis and regenerate normal pancreas and duodenal villi from the wild-type (wt) cells that escape beta-catenin deletion...
  12. pmc Tissue-specific remodeling of the mitochondrial proteome in type 1 diabetic akita mice
    Heiko Bugger
    Division of Endocrinology, Metabolism and Diabetes, and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA
    Diabetes 58:1986-97. 2009
    ..To elucidate the molecular basis for mitochondrial dysfunction, which has been implicated in the pathogenesis of diabetes complications...
  13. pmc Hyperglycemic Ins2AkitaLdlr⁻/⁻ mice show severely elevated lipid levels and increased atherosclerosis: a model of type 1 diabetic macrovascular disease
    Changcheng Zhou
    Laboratory of Biochemical Genetics and Metabolism, Rockefeller University, New York, NY, USA
    J Lipid Res 52:1483-93. 2011
    ..macrovascular disease, we have generated type 1 diabetic Akita mice lacking the low density lipoprotein receptor (Ins2(Akita)Ldlr⁻/⁻). Ins2(Akita)Ldlr⁻/⁻ mice were severely hyperglycemic with impaired glucose tolerance...
  14. pmc Nkx2.2 and Arx genetically interact to regulate pancreatic endocrine cell development and endocrine hormone expression
    Teresa L Mastracci
    Department of Genetics and Development, Russ Berrie Medical Pavilion, Columbia University, 1150 St Nicholas Ave, New York, NY 10032, USA
    Dev Biol 359:1-11. 2011
    ..Together, these experiments identify novel genetic interactions between Nkx2.2 and Arx within the endocrine progenitor cells that ensure the correct specification and regulation of endocrine hormone-producing cells...
  15. ncbi Stabilization of beta-catenin impacts pancreas growth
    Patrick W Heiser
    Diabetes Center, Department of Medicine, University of California, San Francisco, CA 94143, USA
    Development 133:2023-32. 2006
    ..Taken together, these data suggest a previously unappreciated temporal/spatial role for beta-catenin signaling in the regulation of pancreas organ growth...
  16. ncbi The concerted activities of Pax4 and Nkx2.2 are essential to initiate pancreatic beta-cell differentiation
    Junfeng Wang
    Department of Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Dev Biol 266:178-89. 2004
    ..This role of Pax4 appears to be accomplished via its genetic interaction with another homeobox gene, Nkx2.2...
  17. ncbi Beta-catenin is essential for pancreatic acinar but not islet development
    L Charles Murtaugh
    Department of Molecular and Cellular Biology and Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA
    Development 132:4663-74. 2005
    ..Thus, our data are consistent with a crucial role for canonical Wnt signals in acinar lineage specification and differentiation...
  18. pmc Pericyte migration: a novel mechanism of pericyte loss in experimental diabetic retinopathy
    Frederick Pfister
    5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
    Diabetes 57:2495-502. 2008
    ..Hyperglycemia induces angiopoietin-2 (Ang-2) transcription, which modulates capillary pericyte coverage. In this study, we assessed loss of pericyte subgroups and the contribution of Ang-2 to pericyte migration...
  19. pmc A dosage-dependent requirement for Sox9 in pancreatic endocrine cell formation
    Philip A Seymour
    Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697 2300, USA
    Dev Biol 323:19-30. 2008
    ..Our findings therefore suggest that defective endocrine specification might underlie the pancreatic phenotype of individuals with CD...
  20. doi Dendrite remodeling and other abnormalities in the retinal ganglion cells of Ins2 Akita diabetic mice
    Matthew J Gastinger
    Department of Ophthalmology, Penn State Retina Research Group, Penn State College of Medicine, Milton S Hershey Medical Center, Hershey, Pennsylvania 17033, USA
    Invest Ophthalmol Vis Sci 49:2635-42. 2008
    To determine the extent of retinal ganglion cell loss and morphologic abnormalities in surviving ganglion cells in Ins2 Akita/+ diabetic mice.
  21. ncbi Ablation of the glucagon receptor gene increases fetal lethality and produces alterations in islet development and maturation
    Patricia M Vuguin
    Division of Pediatric Endocrinology, Children s Hospital at Montefiore Medical Center, 111 East 210th Street, Bronx, New York 10476, USA
    Endocrinology 147:3995-4006. 2006
    ..These findings suggest that GLU participates in a feedback loop that regulates the proportion of the different endocrine cell types in islets, the number of islets per pancreas, and development of the mature alpha-cell phenotype...
  22. pmc Neurog3 gene dosage regulates allocation of endocrine and exocrine cell fates in the developing mouse pancreas
    Sui Wang
    Program in Developmental Biology and Department of Cell and Developmental Biology, Center for Stem Cell Biology, Vanderbilt University Medical Center, 465 21st Avenue South, Rm 4128, Vanderbilt Medical Center, Nashville, TN 37232, USA
    Dev Biol 339:26-37. 2010
    ..The control of Neurog3+ cell number and the Neurog3 threshold-dependent endocrine differentiation mechanism combine to select a specific proportion of pancreatic progenitor cells to adopt the islet cell fate...
  23. pmc Opposing actions of Arx and Pax4 in endocrine pancreas development
    Patrick Collombat
    Department of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, D 37077 Gottingen, Germany
    Genes Dev 17:2591-603. 2003
    ..We propose that the antagonistic functions of Arx and Pax4 for proper islet cell specification are related to the pancreatic levels of the respective transcripts...
  24. ncbi Regulation of renal fatty acid and cholesterol metabolism, inflammation, and fibrosis in Akita and OVE26 mice with type 1 diabetes
    Gregory Proctor
    Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Diabetes 55:2502-9. 2006
    ....
  25. pmc A modest decrease in endothelial NOS in mice comparable to that associated with human NOS3 variants exacerbates diabetic nephropathy
    Chih Hong Wang
    Department of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC 27599, USA
    Proc Natl Acad Sci U S A 108:2070-5. 2011
    ..inbred females and heterozygous C57BL/6J eNOS(+/-) inbred males carrying the dominant Akita diabetogenic mutation Ins2(C96Y/+)...
  26. ncbi Maternal diabetes adversely affects preovulatory oocyte maturation, development, and granulosa cell apoptosis
    Aimee S Chang
    Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, Washington University in St Louis, St Louis, Missouri 63110 1094, USA
    Endocrinology 146:2445-53. 2005
    ..In addition, there may be dysfunctional or decreased communication in diabetic oocytes, as demonstrated by lower expression of connexin-43...
  27. ncbi Expression of neurogenin3 reveals an islet cell precursor population in the pancreas
    V M Schwitzgebel
    Hormone Research Institute, Department of Pediatrics, and Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA
    Development 127:3533-42. 2000
    ....
  28. pmc The p48 DNA-binding subunit of transcription factor PTF1 is a new exocrine pancreas-specific basic helix-loop-helix protein
    A Krapp
    Swiss Institute for Experimental Cancer Research ISREC, Epalinges Lausanne, Switzerland
    EMBO J 15:4317-29. 1996
    ..Thus the pancreas-specific DNA-binding activity of PTF1 originates from the synthesis of at least one cell-specific component rather than from a cell-specific assembly of more widely distributed proteins...
  29. ncbi Foxa2 is required for the differentiation of pancreatic alpha-cells
    Catherine S Lee
    Department of Genetics and Penn Diabetes Center, University of Pennsylvania School of Medicine, 415 Curie Boulevard, CRB 560 Philadelphia, PA 19104, USA
    Dev Biol 278:484-95. 2005
    ..By marker gene analysis, we show that the expression of the alpha-cell transcription factors Arx, Pax6, and Brn4 does not require Foxa2 in the transcriptional hierarchy governing alpha-cell differentiation...
  30. doi Type 1 diabetic cardiomyopathy in the Akita (Ins2WT/C96Y) mouse model is characterized by lipotoxicity and diastolic dysfunction with preserved systolic function
    Ratnadeep Basu
    Department of Physiology, Rm 474, Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta T6G 2S2, Canada
    Am J Physiol Heart Circ Physiol 297:H2096-108. 2009
    ..We examined the nature and mechanism of the cardiomyopathy in Akita (Ins2(WT/C96Y)) mice, a model of genetic nonobese type 1 diabetes that recapitulates human type 1 diabetes...
  31. pmc Acceleration of type 1 diabetes mellitus in proinsulin 2-deficient NOD mice
    Karine Thébault-Baumont
    Institut National de la Santé et de la Recherche Médicale INSERM U561, Hopital Cochin Saint Vincent de Paul, Paris, France
    J Clin Invest 111:851-7. 2003
    Accumulating evidence favors a role for proinsulin as a key autoantigen in diabetes. In the mouse, two proinsulin isoforms coexist. Most studies point to proinsulin 2 as the major isoform recognized by T cells in the NOD mouse...
  32. ncbi Complications of IgA nephropathy in a non-insulin-dependent diabetes model, the Akita mouse
    Toshiyuki Haseyama
    Department of Hygiene, Akita University School of Medicine, Akita 010 8543, Japan
    Tohoku J Exp Med 198:233-44. 2002
    The Akita mouse, which has a mutation (Cys96Tyr) in the insulin 2 gene (Ins2(Akita)), is a model for diabetes. The male Akita mouse has diabetes, while females develop mild diabetes...
  33. pmc Arx and Nkx2.2 compound deficiency redirects pancreatic alpha- and beta-cell differentiation to a somatostatin/ghrelin co-expressing cell lineage
    Simon Kordowich
    Department of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg, Gottingen, Germany
    BMC Dev Biol 11:52. 2011
    ..2-deficient pancreata. Hence in order to precise the functional link between both factors we performed a comparative analysis of Nkx2.2/Arx single- and double-mutants but also of Pax6-deficient animals...
  34. pmc RNA-mediated gene duplication: the rat preproinsulin I gene is a functional retroposon
    M B Soares
    Mol Cell Biol 5:2090-103. 1985
    ....
  35. pmc PERK (EIF2AK3) regulates proinsulin trafficking and quality control in the secretory pathway
    Sounak Gupta
    Department of Biology, The Huck Institutes of the Life Sciences, Penn State Institute for Diabetes and Obesity, Pennsylvania State University, University Park, Pennsylvania, USA
    Diabetes 59:1937-47. 2010
    ..abnormal cellular phenotype characterized by grossly distended endoplasmic reticulum (ER) and retention of proinsulin. We investigated over synthesis, lack of ER-associated degradation (ERAD), and defects in ER to Golgi ..
  36. pmc Pancreatic neurogenin 3-expressing cells are unipotent islet precursors
    Renaud Desgraz
    Department of Genetic Medicine and Development, University of Geneva Medical School, 1 rue Michel Servet, 1211 Geneva 4, Switzerland
    Development 136:3567-74. 2009
    ..We propose a model whereby Ngn3(+) cells are monotypic (i.e. unipotent) precursors, and use this paradigm to refocus ideas on how cell number and type must be regulated in building complete islets of Langerhans...
  37. pmc Islet-1 is required for the maturation, proliferation, and survival of the endocrine pancreas
    Aiping Du
    Department of Pathology and Laboratory Medicine, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    Diabetes 58:2059-69. 2009
    ....
  38. pmc Pancreatic β-cell Raf-1 is required for glucose tolerance, insulin secretion, and insulin 2 transcription
    Emilyn U Alejandro
    Laboratory of Molecular Signalling in Diabetes, Diabetes Research Group, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada
    FASEB J 25:3884-95. 2011
    ..However, islet insulin protein and insulin 2 mRNA, but not insulin 1 mRNA, were dramatically reduced in Raf-1-knockout mice...
  39. pmc Rfx6 directs islet formation and insulin production in mice and humans
    Stuart B Smith
    Diabetes Center, University of California San Francisco, San Francisco, California 94143, USA
    Nature 463:775-80. 2010
    ..These studies demonstrate a unique position for Rfx6 in the hierarchy of factors that coordinate pancreatic islet development in both mice and humans. Rfx6 could prove useful in efforts to generate beta-cells for patients with diabetes...
  40. pmc Genetic identification of a novel NeuroD1 function in the early differentiation of islet alpha, PP and epsilon cells
    CHRISTINA S CHAO
    University of Colorado at Denver and Health Science Center, Biochemistry and Molecular Genetics Department, Aurora, CO 80045, USA
    Dev Biol 312:523-32. 2007
    ..Furthermore, this study reveals a previously unappreciated early function of NeuroD1 in regulating the specification of alpha, PP and epsilon cells...
  41. ncbi Decreased L-type Ca2+ current in cardiac myocytes of type 1 diabetic Akita mice due to reduced phosphatidylinositol 3-kinase signaling
    Zhongju Lu
    Department of Physiology and Biophysics and the Institute of Molecular Cardiology, Stony Brook University, Stony Brook, New York 11794 8151, USA
    Diabetes 56:2780-9. 2007
    ..Because PI 3-kinases are key mediators of insulin action, we investigated whether LTCC function is affected in diabetic animals due to reduced PI 3-kinase signaling...
  42. pmc Human recombinant ACE2 reduces the progression of diabetic nephropathy
    Gavin Y Oudit
    Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
    Diabetes 59:529-38. 2010
    ..Inhibition of ACE2 function accelerates diabetic kidney injury, whereas renal ACE2 is downregulated in diabetic nephropathy. We examined the ability of human recombinant ACE2 (hrACE2) to slow the progression of diabetic kidney injury...
  43. ncbi The endoplasmic reticulum stress response is stimulated through the continuous activation of transcription factors ATF6 and XBP1 in Ins2+/Akita pancreatic beta cells
    Jun ichi Nozaki
    Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8397, Japan
    Genes Cells 9:261-70. 2004
    The dominant C96Y mutation of one of the two murine insulin genes, Ins2, causes diabetes mellitus in 'Akita' mice. Here we established pancreatic islet beta cell lines from heterozygous mice (Ins2+/Akita)...
  44. pmc Glucagon-like peptide 1 (1-37) converts intestinal epithelial cells into insulin-producing cells
    Atsushi Suzuki
    Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305 8575, Japan
    Proc Natl Acad Sci U S A 100:5034-9. 2003
    ..Our findings suggest that efficient induction of insulin production in intestinal epithelial cells by GLP-1-(1-37) could represent a new therapeutic approach to diabetes mellitus...
  45. pmc Influence of genetic background on albuminuria and kidney injury in Ins2(+/C96Y) (Akita) mice
    Susan B Gurley
    Division of Nephrology, Department of Medicine, Duke University and Durham Veterans Affairs Medical Centers, Durham, North Carolina, USA
    Am J Physiol Renal Physiol 298:F788-95. 2010
    Previous studies have shown that Akita mice bearing the Ins2(+/C96Y) mutation have significant advantages as a type I diabetes platform for developing models of diabetic nephropathy (DN; Gurley SB, Clare SE, Snow KP, Hu A, Meyer TW, ..
  46. ncbi PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum
    M F Offield
    Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232 2175, USA
    Development 122:983-95. 1996
    ..These results offer additional insight into the role of pdx-1 in the determination and differentiation of the posterior foregut, particularly regarding the proliferation and differentiation of the pancreatic progenitors...
  47. ncbi Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of beta-cell formation in the pancreas
    M Sander
    Hormone Research Institute, University of California San Francisco, San Francisco, CA 94143 0534, USA
    Development 127:5533-40. 2000
    ..Together, these experiments reveal two independently controlled pathways for beta-cell differentiation, and place Nkx6.1 downstream of Nkx2.2 in the major pathway of beta-cell differentiation...
  48. ncbi MicroRNA expression is required for pancreatic islet cell genesis in the mouse
    Francis C Lynn
    Diabetes Center, Hormone Research Institute, University of California San Francisco, 513 Parnassus Ave, San Francisco, CA 94143 0534, USA
    Diabetes 56:2938-45. 2007
    ..We tested the hypothesis that microRNAs (miRNAs), which limit gene expression through posttranscriptional silencing, modulate the gene expression cascades involved in pancreas development...
  49. ncbi PERK EIF2AK3 control of pancreatic beta cell differentiation and proliferation is required for postnatal glucose homeostasis
    Wei Zhang
    Department of Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA
    Cell Metab 4:491-7. 2006
    ..exhibit severe defects in fetal/neonatal beta cell proliferation and differentiation, resulting in low beta cell mass, defects in proinsulin trafficking, and abrogation of insulin secretion that culminate in permanent neonatal diabetes.
  50. ncbi The Pax4 gene is essential for differentiation of insulin-producing beta cells in the mammalian pancreas
    B Sosa-Pineda
    Max Planck Institute for Biophysical Chemistry, Gottingen, Germany
    Nature 386:399-402. 1997
    ..A default pathway would explain the elevated number of alpha cells in the absence of Pax4...
  51. pmc Mapping of murine diabetogenic gene mody on chromosome 7 at D7Mit258 and its involvement in pancreatic islet and beta cell development during the perinatal period
    T Kayo
    Department of Hygiene, Akita University School of Medicine, Akita 010, Japan
    J Clin Invest 101:2112-8. 1998
    Mutation of the murine maturity-onset diabetes mellitus of the young (Mody) locus induces diabetes, but the effects of its homozygosity on the pancreas remain unknown...
  52. pmc A switch from MafB to MafA expression accompanies differentiation to pancreatic beta-cells
    Wataru Nishimura
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, MA 02215, USA
    Dev Biol 293:526-39. 2006
    ..Thus, this redundancy in the function and expression of the large-Maf factors may explain the normal islet morphology observed in the MafA knockout mice at birth...
  53. pmc Control of precursor maturation and disposal is an early regulative mechanism in the normal insulin production of pancreatic β-cells
    Jie Wang
    Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America
    PLoS ONE 6:e19446. 2011
    The essential folding and maturation process of proinsulin in β-cells is largely uncharacterized...
  54. ncbi Ghrelin is a novel target of Pax4 in endocrine progenitors of the pancreas and duodenum
    Qian Wang
    Department of Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Dev Dyn 237:51-61. 2008
    ..Together, our data further support the notion that Pax4 activity is necessary to establish appropriate patterns of gene expression in endocrine progenitors of the digestive tract...
  55. pmc Preferential reduction of beta cells derived from Pax6-MafB pathway in MafB deficient mice
    Wataru Nishimura
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, USA
    Dev Biol 314:443-56. 2008
    ..Thus, Pax6 acts upstream of MafB, which in turn may trigger the expression of insulin and regulate the PDX-1 and MafA expression required for beta-cell maturation...
  56. pmc Rfx6 is an Ngn3-dependent winged helix transcription factor required for pancreatic islet cell development
    Josselin Soyer
    Institute of Genetics and Molecular and Cell Biology IGBMC, INSERM U 964, CNRS UMR7104, University of Strasbourg, Illkirch, France
    Development 137:203-12. 2010
    ..By contrast, beta cells, whose number is only slightly reduced, were no longer clustered in a compact islet. These data unveil Rfx6 as a novel regulator of islet cell development...
  57. pmc Insulin gene mutations as a cause of permanent neonatal diabetes
    Julie Støy
    Department of Medicine, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 104:15040-4. 2007
    ..regions of the preproinsulin molecule, and we predict that they prevent normal folding and progression of proinsulin in the insulin secretory pathway...
  58. pmc Recovery from diabetes in mice by beta cell regeneration
    Tomer Nir
    Department of Cellular Biochemistry and Human Genetics, Hebrew University Hadassah Medical School, Jerusalem, Israel
    J Clin Invest 117:2553-61. 2007
    ..These results suggest that regenerative therapy for type 1 diabetes may be achieved if autoimmunity is halted using regeneration-compatible drugs...
  59. doi Cell adhesion molecule 1 is a novel pancreatic-islet cell adhesion molecule that mediates nerve-islet cell interactions
    Yu Ichiro Koma
    Division of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan
    Gastroenterology 134:1544-54. 2008
    ..An immunohistochemical screen showed that CADM1 is expressed in pancreatic islets. Here, we determined the cell types expressing CADM1 and examined its role in nerve-islet cell interactions...
  60. doi Comparison of murine embryonic pancreatic development in vitro and in vivo
    Fengxia Ma
    State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences, Tianjin, China
    Pancreas 40:1012-7. 2011
    ..The purpose of the present study was to compare the development of murine embryonic pancreas in vitro and in vivo...
  61. pmc Loss of bradykinin signaling does not accelerate the development of cardiac dysfunction in type 1 diabetic akita mice
    Adam R Wende
    Program in Molecular Medicine and Division of Endocrinology, Metabolism, and Diabetes, University of Utah, School of Medicine, Salt Lake City, Utah 84112, USA
    Endocrinology 151:3536-42. 2010
    ..B1 and B2 receptors (B1RB2R(-/-)) in the context of the Akita model of insulin-deficient type 1 diabetes (Ins2(Akita/+))...
  62. doi Proinsulin maturation disorder is a contributor to the defect of subsequent conversion to insulin in β-cells
    Jie Wang
    Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA
    Biochem Biophys Res Commun 411:150-5. 2011
    ..Recently, we have found proinsulin is an aggregation-prone molecule inherent with a low relative folding rate and maintains a homeostatic balance ..
  63. ncbi Cadherins regulate aggregation of pancreatic beta-cells in vivo
    U Dahl
    Department of Microbiology, University of Umea, Sweden
    Development 122:2895-902. 1996
    ..Thus, we have for the first time shown in vivo that cadherins regulate adhesive properties of beta-cells which are essential for the aggregation of endocrine cells into islets...
  64. pmc Pancreas-specific deletion of mouse Gata4 and Gata6 causes pancreatic agenesis
    Shouhong Xuan
    Department of Genetics and Development, Columbia University, New York, New York 10032, USA
    J Clin Invest 122:3516-28. 2012
    ....
  65. pmc Integrin α1/Akita double-knockout mice on a Balb/c background develop advanced features of human diabetic nephropathy
    Ling Yu
    Division of Nephrology, Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA
    Kidney Int 81:1086-97. 2012
    ..Thus, the integrin α1KOAkitaKO Balb/c mouse represents a promising model presenting with most features of human diabetic nephropathy...
  66. pmc Sigma receptor 1 modulates endoplasmic reticulum stress in retinal neurons
    Yonju Ha
    Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA 30912 2000, USA
    Invest Ophthalmol Vis Sci 52:527-40. 2011
    ..To investigate the mechanism of σ receptor 1 (σR1) neuroprotection in retinal neurons...
  67. ncbi Differential expression and imprinting status of Ins1 and Ins2 genes in extraembryonic tissues of laboratory mice
    L Deltour
    Departement Genetique, Developpement et Pathologie Moleculaire, Institut Cochin, INSERM U567, CNRS UMR 8104, Universite Rene Descartes, 75014 Paris, France
    Gene Expr Patterns 5:297-300. 2004
    There are two functional insulin genes in the mouse genome. The Ins2 gene is imprinted and expressed monoallelically from the paternal allele in the yolk sac. In the present study we have re-examined the imprinting status of Ins1...
  68. ncbi Expression pattern of IAPP and prohormone convertase 1/3 reveals a distinctive set of endocrine cells in the embryonic pancreas
    Maria E Wilson
    UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143 0534, USA
    Mech Dev 115:171-6. 2002
    ..The early production of atypical peptide hormones by these cells suggests that they could play an important role locally or systemically in the development of the embryo...
  69. doi Intravenous administration of proinsulin 1 or 2-expressing fiber-mutant recombinant adenovirus vector protects against the development of diabetes in NOD mice
    Katsumi Yamada
    Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
    Ann N Y Acad Sci 1150:183-6. 2008
    ..Pins1-RGD and that of Ad.Pins2-RGD. Our study suggests that systemic administration of fiber-mutant adenovirus vectors, which induce transient expression of proinsulin, may be applicable to a gene therapy inducing tolerance to insulin.
  70. pmc Dynamic regulation of Pdx1 enhancers by Foxa1 and Foxa2 is essential for pancreas development
    Nan Gao
    Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Genes Dev 22:3435-48. 2008
    ..Thus, the regulation of Pdx1 expression by Foxa1 and Foxa2 is a key early event controlling the expansion and differentiation of the pancreatic primordia...
  71. ncbi Sequence-ready 1-Mb YAC, BAC and cosmid contigs covering the distal imprinted region of mouse chromosome 7
    R Kato
    Department of Integrated Genetics, National Institute of Genetics and Graduate University for Advanced Studies, Mishima, Shizuoka, Japan
    DNA Res 6:401-5. 1999
    ....
  72. ncbi Regulation of pancreas development by hedgehog signaling
    M Hebrok
    Department of Molecular and Cellular Biology and Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA
    Development 127:4905-13. 2000
    ..Defects in hedgehog signaling may lead to congenital pancreatic malformations and glucose intolerance...
  73. pmc Targeted disruption of the Chop gene delays endoplasmic reticulum stress-mediated diabetes
    Seiichi Oyadomari
    Department of Molecular Genetics, Kumamoto University School of Medicine, Kumamoto, Japan
    J Clin Invest 109:525-32. 2002
    ..The Akita mouse, which carries a conformation-altering missense mutation (Cys96Tyr) in Insulin 2, likewise exhibits hyperglycemia and a reduced beta cell mass...
  74. ncbi Impact of genetic background on nephropathy in diabetic mice
    Susan B Gurley
    Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, NC, USA
    Am J Physiol Renal Physiol 290:F214-22. 2006
    ..Thus, among the strains and models tested, the DBA/2 genetic background and the Akita (Ins2(+/C96Y)) model may be the most useful platforms for model development.
  75. pmc MafB is required for islet beta cell maturation
    Isabella Artner
    Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, 723 Light Hall, Nashville, TN 37232, USA
    Proc Natl Acad Sci U S A 104:3853-8. 2007
    ..These results demonstrate that MafB plays a previously uncharacterized role by regulating transcription of key factors during development that are required for the production of mature alpha and beta cells...
  76. pmc Neuronatin, a downstream target of BETA2/NeuroD1 in the pancreas, is involved in glucose-mediated insulin secretion
    Khoi Chu
    Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Diabetes 54:1064-73. 2005
    ..These results suggest for the first time an important role for NNAT in insulin secretion and for proper beta-cell function...
  77. ncbi The morphogenesis of the pancreatic mesenchyme is uncoupled from that of the pancreatic epithelium in IPF1/PDX1-deficient mice
    U Ahlgren
    Department of Microbiology, University of Umea, Sweden
    Development 122:1409-16. 1996
    ..Together these data provide evidence that PDX-1 acts cell autonomously and that the lack of a pancreas in the pdx1-/- mice is due to a defect in the pancreatic epithelium...
  78. pmc Type 1 diabetic akita mouse hearts are insulin sensitive but manifest structurally abnormal mitochondria that remain coupled despite increased uncoupling protein 3
    Heiko Bugger
    Division of Endocrinology, Metabolism, and Diabetes, Program in Human Molecular Biology and Genetics, University of Utah School of Medicine, Salt Lake City, Utah, USA
    Diabetes 57:2924-32. 2008
    ..We hypothesized that mitochondrial uncoupling may also contribute to reduced cardiac efficiency and contractile dysfunction in the type 1 diabetic Akita mouse model (Akita)...
  79. pmc Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation
    Liqin Zhu
    Department of Developmental Neurobiology, St Jude Children s Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA
    Nature 457:603-7. 2009
    ..Our data indicate that Prom1 marks stem cells in the adult small intestine that are susceptible to transformation into tumours retaining a fraction of mutant Prom1(+) tumour cells...
  80. doi ATF4-mediated induction of 4E-BP1 contributes to pancreatic beta cell survival under endoplasmic reticulum stress
    Suguru Yamaguchi
    Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980 8575, Japan
    Cell Metab 7:269-76. 2008
    ..Thus, 4E-BP1 induction contributes to the maintenance of beta cell homeostasis during ER stress and is a potential therapeutic target for diabetes...
  81. pmc Role of SREBP-1 in the development of parasympathetic dysfunction in the hearts of type 1 diabetic Akita mice
    Ho Jin Park
    Tufts Medical Center, Molecular Cardiology Research Institute, 750 Washington St, Box 8486, Boston, MA 02111, USA
    Circ Res 105:287-94. 2009
    ..Sterol regulatory element binding protein-1 (SREBP-1) is a lipid-sensitive transcription factor...
  82. ncbi Orpk mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organization
    David A Cano
    Diabetes Center, Department of Medicine, University of California, San Francisco, CA 94143, USA
    Development 131:3457-67. 2004
    ..Thus, polaris and primary cilia function are required for the maturation and maintenance of proper tissue organization in the pancreas...
  83. ncbi The fringe molecules induce endocrine differentiation in embryonic endoderm by activating cMyt1/cMyt3
    Yanwen Xu
    Vanderbilt University, Department of Cell and Developmental Biology, Nashville, TN 37232, USA
    Dev Biol 297:340-9. 2006
    ..These results suggest that Mfng-mediated repression of Notch signaling could serve as a trigger for endocrine islet differentiation...
  84. ncbi MafB: an activator of the glucagon gene expressed in developing islet alpha- and beta-cells
    Isabella Artner
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Diabetes 55:297-304. 2006
    ..These results indicate that MafB is not only important to islet alpha-cell function but may also be involved in regulating genes required in both endocrine alpha- and beta-cell differentiation...
  85. ncbi Attenuated Wnt signaling perturbs pancreatic growth but not pancreatic function
    Stella Papadopoulou
    Umeå Centre for Molecular Medicine, University of Umea, S 901 87 Umea, Sweden
    Diabetes 54:2844-51. 2005
    ..Collectively, our data provide evidence that Wnt signaling is required for pancreatic growth but not adult beta-cell function...
  86. pmc Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice
    Maki Nakayama
    Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    Nature 435:220-3. 2005
    ..Here we show that the proinsulin/insulin molecules have a sequence that is a primary target of the autoimmunity that causes diabetes of the non-..
  87. pmc A mutation in the insulin 2 gene induces diabetes with severe pancreatic beta-cell dysfunction in the Mody mouse
    J Wang
    Department of Molecular Medicine, Gunma University, Maebashi, Japan
    J Clin Invest 103:27-37. 1999
    ..no gross defect in the transcription from the wild-type insulin 2 allele or two alleles of insulin 1, levels of proinsulin and insulin were profoundly diminished in the beta cells of Mody mice, suggesting that the number of wild-type (..
  88. pmc Matrix metalloproteinases 2 and 9 are dispensable for pancreatic islet formation and function in vivo
    Sabina E Perez
    Diabetes Center, Department of Medicine, University of California, San Francisco, California, 94143 0573, USA
    Diabetes 54:694-701. 2005
    ..However, islet formation is unaffected in transgenic mice with modified tissue inhibitor of metalloproteinase-1 (TIMP1) levels, suggesting that MMP activity may contribute little to islet morphogenesis in vivo...
  89. ncbi Dependence of self-tolerance on TRAF6-directed development of thymic stroma
    Taishin Akiyama
    Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    Science 308:248-51. 2005
    ..Engraftment of thymic stroma of TRAF6(-/-) embryos into athymic nude mice induced autoimmunity. Thus, TRAF6 directs the development of thymic stroma and represents a critical point of regulation for self-tolerance and autoimmunity...
  90. ncbi FGF10 signaling maintains the pancreatic progenitor cell state revealing a novel role of Notch in organ development
    Gitte Anker Norgaard
    Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Dev Biol 264:323-38. 2003
    ..These data suggest that FGF10 signaling serves to integrate cell growth and terminal differentiation at the level of Notch activation, revealing a novel second role of this key signaling system during pancreatic development...
  91. ncbi Sequence and functional comparison in the Beckwith-Wiedemann region: implications for a novel imprinting centre and extended imprinting
    S Engemann
    Max Planck Institut fur Molekulare Genetik, Ihnestrasse 73, D 14195 Berlin, Germany
    Hum Mol Genet 9:2691-706. 2000
    ..One of the genes outside the cluster, Obph1, is imprinted in mouse placenta indicating that at least in extra-embryonic tissues the imprinting cluster extends into a larger domain...
  92. ncbi Dominant negative pathogenesis by mutant proinsulin in the Akita diabetic mouse
    Tetsuro Izumi
    Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan
    Diabetes 52:409-16. 2003
    ..Although the results of our previous study suggested that the mutant proinsulin 2 is misfolded and blocked in the transport from the endoplasmic reticulum to the Golgi apparatus, its dominant ..
  93. ncbi ErbB signaling regulates lineage determination of developing pancreatic islet cells in embryonic organ culture
    Mari Anne Huotari
    Biomedicum Helsinki, Program for Developmental and Reproductive Biology and Haartman Institute, University of Helsinki, Helsinki 00014, Finland
    Endocrinology 143:4437-46. 2002
    ..BTC, acting through EGF-R/erbB-1, is important for the differentiation of beta-cells. This could be applied in the targeted differentiation of stem cells into insulin-producing cells...
  94. ncbi Notch/Rbp-j signaling prevents premature endocrine and ductal cell differentiation in the pancreas
    Junji Fujikura
    Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara cho, Sakyo ku, Kyoto 606 8507, Japan
    Cell Metab 3:59-65. 2006
    ..Thus, our analyses indicate that Notch/Rbp-j signaling prevents premature differentiation of pancreatic progenitor cells into endocrine and ductal cells during early development of the pancreas...
  95. pmc Conditional expression of Smad7 in pancreatic beta cells disrupts TGF-beta signaling and induces reversible diabetes mellitus
    Nora G Smart
    Department of Developmental Biology, Stanford University School of Medicine, Stanford, California, USA
    PLoS Biol 4:e39. 2006
    ..Thus, our studies reveal that TGF-beta signaling is crucial for establishing and maintaining defining features of mature pancreatic beta cells...
  96. pmc Senescence-associated phenotypes in Akita diabetic mice are enhanced by absence of bradykinin B2 receptors
    Masao Kakoki
    Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7525, USA
    J Clin Invest 116:1302-9. 2006
    ..in B2 receptor-null mice, clearly apparent in mice diabetic because of a dominant mutation (Akita) in the Ins2 gene, and most obvious in Akita diabetic plus B2 receptor-null mice...
  97. ncbi Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to arrested differentiation of pancreatic beta cells
    L Sussel
    Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco, CA 94143, USA
    Development 125:2213-21. 1998
    ..1. We propose that Nkx2.2 is required for the final differentiation of pancreatic beta cells, and in its absence, beta cells are trapped in an incompletely differentiated state...
  98. ncbi The FoxM1 transcription factor is required to maintain pancreatic beta-cell mass
    Hongjie Zhang
    Departments of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Mol Endocrinol 20:1853-66. 2006
    ..These results suggest that mechanisms regulating embryonic beta-cell proliferation differ from those used postnatally to maintain the differentiated cell population...
  99. ncbi Fgf10 is essential for maintaining the proliferative capacity of epithelial progenitor cells during early pancreatic organogenesis
    A Bhushan
    INSERM 457, Hospital Robert Debre, 75019 Paris, France
    Development 128:5109-17. 2001
    ..These results indicate that Fgf10 signalling is required for the normal development of the pancreas and should prove useful in devising methods to expand pancreatic progenitor cells...
  100. ncbi Developmental biology of the pancreas
    J M Slack
    Department of Zoology, Oxford University, UK
    Development 121:1569-80. 1995
    ....
  101. ncbi The cut-homeodomain transcriptional activator HNF-6 is coexpressed with its target gene HNF-3 beta in the developing murine liver and pancreas
    F Rausa
    Department of Biochemistry and Molecular Biology, University of Illinois at Chicago 60612 7334, USA
    Dev Biol 192:228-46. 1997
    ..We discuss these expression patterns with respect to specification of hepatocytes and differentiation of the endocrine and exocrine pancreas...

Research Grants84

  1. A Novel Tool to Understand Insulin Production and Failure in Pancreatic beta-Cell
    Israel Hodish; Fiscal Year: 2007
    ..ER stress includes misfolding of proinsulin, the beta cell's major secretory protein product - the precursor in insulin biosynthesis...
  2. GLUCOKINASE GENE EXPRESSION IN PANCREATIC BETA CELL
    Mark Magnuson; Fiscal Year: 2001
    ..In humans, mutations in this enzyme cause both maturity onset diabetes of youth, type 2 (MODY-2) and persistant hyperinsulinemic hypoglycemia of infancy (PHHI)...
  3. Coordinating Center for Beta Cell Biology Consortium
    Mark Magnuson; Fiscal Year: 2007
    ....
  4. Coordinating Center for Beta Cell Biology Consortium
    Mark Magnuson; Fiscal Year: 2007
    ..abstract_text> ..
  5. GLUCOKINASE GENE EXPRESSION IN PANCREATIC BETA CELL
    Mark Magnuson; Fiscal Year: 2005
    ..In Aim 2 we will establish true mouse models for PHHI and MODY-2 in order to correlate changes in enzyme kinetics with insuIin secretion and glucose homeostasis...
  6. GLUCOKINASE GENE EXPRESSION IN THE PANCREATIC BETA CELL
    Mark Magnuson; Fiscal Year: 1993
    ..These factors will be studied further using mobility shift and methylation interference assays. Efforts to purify and clone one of these factors will be initiated...
  7. REGULATORY CASCADES IN GASTROINTESTINAL PROLIFERATION
    KLAUS KAESTNER; Fiscal Year: 2006
    ..Together, these studies will further our understanding of the regulatory circuits that control gastrointestinal proliferation in normal development and carcinogenesis. ..
  8. Foxm 1b endocrine pancreas growth and regeneration
    Maureen Gannon; Fiscal Year: 2007
    ..A thorough understanding of Foxm1 regulation of ( cell mass may lead to strategies for maintaining ( cell mass and enhancing ( cell proliferation in diabetics. ..
  9. Analysis of neural retina transport function
    Sylvia Smith; Fiscal Year: 2007
    ..We will determine whether the Hcy-induced retinopathy in cbs mutant mice is due solely to lack of adequate folate or is due to a complexity of cellular insults including oxidative stress, excitotoxic damage, ER stress, and DNA damage. ..
  10. STUDY OF DIABETIC RETINOPATHY
    Timothy Kern; Fiscal Year: 2007
    ..Steps downstream of peroxynitrite and prostaglandin production responsible for hyperglycemia-mediated death of retinal capillary cells then will be investigated. ..
  11. Development of C57BL/6 ES cell technology for high thoughput use.
    KLAUS KAESTNER; Fiscal Year: 2007
    ....
  12. Nutrition, Early Development and Glucose Metabolism
    Patricia Vuguin; Fiscal Year: 2007
    ..abstract_text> ..
  13. HNF6 Function in the Pancreatic Endocrine Lineage
    Maureen A Gannon; Fiscal Year: 2010
    ..e. is HNF6 needed only at early stages of endocrine specification, or is it required continuously during embryogenesis for terminal differentiation and acquisition of mature function. ..
  14. TRANSCRIPTIONAL CONTROL OF PANCREATIC DEVELOPMENT
    Klaus H Kaestner; Fiscal Year: 2010
    ..in the etiology of diabetes is exemplified by the fact that five of the six known forms of monogenic diabetes (MODY) result from mutations in genes encoding these factors...
  15. Diabetic retinopathy: sigma receptor 1 (??R1) as a novel therapeutic target.
    Sylvia B Smith; Fiscal Year: 2010
    ..The proposed project will extend these findings to understand the mechanism of this protection with the ultimate goal of determining whether (+)- pentazocine may be useful clinically for retinopathy in humans. ..
  16. Epigenomic Profiling of Normal and Diabetic Pancreatic Beta-Cells
    Klaus H Kaestner; Fiscal Year: 2010
    ..We will determine the "epigenetic", that is not mutation based, changes in the genome of the diabetic beta-cell that cause it to fail. This work will identify new potential drug targets for the treatment of type 2 diabetes. ..
  17. REGULATORY CASCADES IN GASTROINTESTINAL PROLIFERATION
    Klaus H Kaestner; Fiscal Year: 2010
    ..Together, this proposal will further our understanding of GI development and cancer, and allow for the development of novel diagnostic and possibly therapeutic tools in the future. ..
  18. TRANSCRIPTIONAL CONTROL OF PANCREATIC DEVELOPMENT
    Klaus H Kaestner; Fiscal Year: 2010
    ..in the etiology of diabetes is exemplified by the fact that five of the six known forms of monogenic diabetes (MODY) result from mutations in genes encoding these factors...
  19. Mechanisms of endoderm specification along the A-P axis.
    James M Wells; Fiscal Year: 2010
    ..Additionally, this information should allow us to coax embryonic stem cells into becoming important transplantable derivatives of endoderm, such as insulin-producing beta cells to treat patients with Type 1 diabetes. ..
  20. Analysis of neural retina transport function
    Sylvia Smith; Fiscal Year: 2009
    ..We will determine whether the Hcy-induced retinopathy in cbs mutant mice is due solely to lack of adequate folate or is due to a complexity of cellular insults including oxidative stress, excitotoxic damage, ER stress, and DNA damage. ..
  21. In vivo study of diabetic hyperglycemia and inflammation
    Robert Gyurko; Fiscal Year: 2009
    ..Moreover, findings on novel lipid inhibitors of inflammation will be important in evaluating the therapeutic potential of these compounds in resolving inflammation in periodontal and other inflammations. ..
  22. Foxm 1b endocrine pancreas growth and regeneration
    Maureen Gannon; Fiscal Year: 2009
    ..A thorough understanding of Foxml regulation of 3 cell mass may lead to strategies for maintaining 3 cell mass and enhancing 3 cell proliferation in diabetics. ..
  23. FUNCTIONAL GENOMICS OF THE BETA-CELL
    KLAUS KAESTNER; Fiscal Year: 2007
    ..The new resources generated through this project will be made available to the NIDDK-funded biotechnology centers and the diabetes research community at large. ..
  24. REGULATORY CASCADES IN GASTROINTESTINAL PROLIFERATION
    Klaus H Kaestner; Fiscal Year: 2010
    ..Together, this proposal will further our understanding of GI development and cancer, and allow for the development of novel diagnostic and possibly therapeutic tools in the future. ..
  25. FUNCTIONAL GENOMICS OF THE BETA-CELL
    KLAUS KAESTNER; Fiscal Year: 2006
    ..The new resources generated through this project will be made available to the NIDDK-funded biotechnology centers and the diabetes research community at large. ..
  26. FUNCTION OF A GROWTH INDUCED GENE IN LIVER REGENERATION
    KLAUS KAESTNER; Fiscal Year: 2003
    ....
  27. REGULATORY CASCADES IN GASTROINTESTINAL PROLIFERATION
    KLAUS KAESTNER; Fiscal Year: 2001
    ..Together, these studies will further our understanding of the regulatory circuits that control gastrointestinal proliferation in normal development and carcinogenesis. ..
  28. DIABETIC RETINOPATHY
    Timothy Kern; Fiscal Year: 1999
    ....
  29. Mechanisms of endoderm specification along the A-P axis
    James Wells; Fiscal Year: 2009
    ..Additionally, this information should allow us to coax embryonic stem cells into becoming important transplantable derivatives of endoderm, such as insulin-producing beta cells to treat patients with Type 1 diabetes. ..
  30. Expression profiling of human islets
    KLAUS KAESTNER; Fiscal Year: 2006
    ....
  31. Nitric Oxide Defense Against Porphyromonas gingivalis
    Robert Gyurko; Fiscal Year: 2006
    ..He is applying for the NIDCR Scholar Development and Faculty Transition Award to pursue scientific career as an independent investigator at Boston University School of Dental Medicine. ..
  32. TRANSCRIPTIONAL CONTROL OF PANCREATIC DEVELOPMENT
    KLAUS KAESTNER; Fiscal Year: 2007
    ..These regulatory proteins also play a major role in the etiology of diabetes as evidenced by the fact that all MODY genes with the exception of MODY2 encode transcription factors...
  33. Diabetic retinopathy: aR1 as a novel therapeutic target
    Sylvia Smith; Fiscal Year: 2007
    ..AIM 3 will test the hypothesis that sigmaR1 agonists will be protective against RGC death characteristic of diabetic retinopathy. ..