insulin

Summary

Gene Symbol: insulin
Description: insulin
Alias: IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10, insulin, preproinsulin, proinsulin
Species: human

Top Publications

  1. pmc Global haplotype diversity in the human insulin gene region
    John D H Stead
    Department of Genetics, University of Leicester, Leicester LE1 7RH, UK
    Genome Res 13:2101-11. 2003
  2. ncbi Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope
    Sally C Kent
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 435:224-8. 2005
  3. ncbi The insulin gene in type 1 diabetes
    Alberto Pugliese
    Immunogenetics Program, Diabetes Research Institute, Miller School of Medecine, University of Miami, Miami, Florida 33136, USA
    IUBMB Life 57:463-8. 2005
  4. pmc Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis
    Intza Garin
    Endocrinology and Diabetes Research Group, Hospital de Cruces, Barakaldo, 48903 Spain
    Proc Natl Acad Sci U S A 107:3105-10. 2010
  5. ncbi Sequence of the human insulin gene
    G I Bell
    Nature 284:26-32. 1980
  6. pmc Myo1c binding to submembrane actin mediates insulin-induced tethering of GLUT4 vesicles
    Shlomit Boguslavsky
    Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
    Mol Biol Cell 23:4065-78. 2012
  7. ncbi Type 1 diabetes risk analysis on dried blood spot samples from population-based newborns: design and feasibility of an unselected case-control study
    Stefanie Eising
    Steno Diabetes Centre, Gentofte, Denmark
    Paediatr Perinat Epidemiol 21:507-17. 2007
  8. pmc Allele-specific recognition of the 3' splice site of INS intron 1
    Jana Kralovicova
    Division of Human Genetics, University of Southampton School of Medicine, MP808, Southampton, SO16 6YD, UK
    Hum Genet 128:383-400. 2010
  9. pmc Insulin-stimulated GLUT4 protein translocation in adipocytes requires the Rab10 guanine nucleotide exchange factor Dennd4C
    Hiroyuki Sano
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Biol Chem 286:16541-5. 2011
  10. ncbi Insulin and IGF-1 regulate the expression of the pituitary tumor transforming gene (PTTG) in breast tumor cells
    Alvin D Thompson
    Department of Biochemistry and Molecular Biology, James Graham Brown Cancer Center, University of Louisville, 580 South Preston, Baxter II, 324, Kentucky 40202, USA
    FEBS Lett 579:3195-200. 2005

Research Grants

  1. Randal J Kaufman; Fiscal Year: 2014
  2. Randal J Kaufman; Fiscal Year: 2016
  3. Douglas R Cavener; Fiscal Year: 2016
  4. Peter Arvan; Fiscal Year: 2016
  5. Low-cost proinsulin-transferrin fusion protein in rice for treatment of diabetes
    Deshui Zhang; Fiscal Year: 2013
  6. JAMES RUSSELL SOWERS; Fiscal Year: 2015
  7. ENGINEERED GLUCOSE METABOLISM IN INSULIN SECRETING CELLS
    Christopher B Newgard; Fiscal Year: 2010
  8. Christopher J Rhodes; Fiscal Year: 2014
  9. METABOLIC CONTROL OF PROINSULIN BIOSYNTHESIS TRANSLATION
    Christopher Rhodes; Fiscal Year: 2009
  10. Rohit N Kulkarni; Fiscal Year: 2016

Detail Information

Publications303 found, 100 shown here

  1. pmc Global haplotype diversity in the human insulin gene region
    John D H Stead
    Department of Genetics, University of Leicester, Leicester LE1 7RH, UK
    Genome Res 13:2101-11. 2003
    The insulin minisatellite (INS VNTR) has been intensively analyzed due to its associations with diseases including diabetes...
  2. ncbi Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope
    Sally C Kent
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 435:224-8. 2005
    In autoimmune type 1 diabetes, pathogenic T lymphocytes are associated with the specific destruction of insulin-producing beta-islet cells. Identification of the autoantigens involved in triggering this process is a central question...
  3. ncbi The insulin gene in type 1 diabetes
    Alberto Pugliese
    Immunogenetics Program, Diabetes Research Institute, Miller School of Medecine, University of Miami, Miami, Florida 33136, USA
    IUBMB Life 57:463-8. 2005
    b>Insulin is a key autoantigen in the autoimmune process leading to the development of type 1 diabetes...
  4. pmc Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis
    Intza Garin
    Endocrinology and Diabetes Research Group, Hospital de Cruces, Barakaldo, 48903 Spain
    Proc Natl Acad Sci U S A 107:3105-10. 2010
    Heterozygous coding mutations in the INS gene that encodes preproinsulin were recently shown to be an important cause of permanent neonatal diabetes...
  5. ncbi Sequence of the human insulin gene
    G I Bell
    Nature 284:26-32. 1980
    The human insulin gene contains two intervening sequences, one is within the region transcribed into the 5'-untranslated segment of the mRNA and the other interrupts the C-peptide encoding region...
  6. pmc Myo1c binding to submembrane actin mediates insulin-induced tethering of GLUT4 vesicles
    Shlomit Boguslavsky
    Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
    Mol Biol Cell 23:4065-78. 2012
    GLUT4-containing vesicles cycle between the plasma membrane and intracellular compartments. Insulin promotes GLUT4 exocytosis by regulating GLUT4 vesicle arrival at the cell periphery and its subsequent tethering, docking, and fusion ..
  7. ncbi Type 1 diabetes risk analysis on dried blood spot samples from population-based newborns: design and feasibility of an unselected case-control study
    Stefanie Eising
    Steno Diabetes Centre, Gentofte, Denmark
    Paediatr Perinat Epidemiol 21:507-17. 2007
    ..It combined genetic, immunological and demographic data to develop prediction algorithms. It also provided a resource for future studies in which new genetic markers can be included as they are identified...
  8. pmc Allele-specific recognition of the 3' splice site of INS intron 1
    Jana Kralovicova
    Division of Human Genetics, University of Southampton School of Medicine, MP808, Southampton, SO16 6YD, UK
    Hum Genet 128:383-400. 2010
    Genetic predisposition to type 1 diabetes (T1D) has been associated with a chromosome 11 locus centered on the proinsulin gene (INS) and with differential steady-state levels of INS RNA from T1D-predisposing and -protective haplotypes...
  9. pmc Insulin-stimulated GLUT4 protein translocation in adipocytes requires the Rab10 guanine nucleotide exchange factor Dennd4C
    Hiroyuki Sano
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Biol Chem 286:16541-5. 2011
    b>Insulin-stimulated translocation of the glucose transporter GLUT4 to the cell surface in fat and muscle cells is the basis for insulin-stimulated glucose transport...
  10. ncbi Insulin and IGF-1 regulate the expression of the pituitary tumor transforming gene (PTTG) in breast tumor cells
    Alvin D Thompson
    Department of Biochemistry and Molecular Biology, James Graham Brown Cancer Center, University of Louisville, 580 South Preston, Baxter II, 324, Kentucky 40202, USA
    FEBS Lett 579:3195-200. 2005
    ..Here, we report the effects of insulin and the insulin like growth factor-1 (IGF-1) on the expression of PTTG...
  11. ncbi Fetal growth is increased by maternal type 1 diabetes and HLA DR4-related gene interactions
    M Hummel
    Institute of Diabetes Research and Academic Hospital Schwabing, Kolner Platz 1, 80804, Munchen, Germany
    Diabetologia 50:850-8. 2007
    ..The aim of this study was to determine whether HLA DR4 was associated with increased birthweight in a maternal diabetes environment and whether effects persisted during early childhood...
  12. doi Insulin stimulates hepatic low density lipoprotein receptor-related protein 1 (LRP1) to increase postprandial lipoprotein clearance
    Alexander Laatsch
    Department of Biochemistry and Molecular Biology II Molecular Cell Biology, University Medical Center Hamburg Eppendorf, Hamburg, Germany
    Atherosclerosis 204:105-11. 2009
    While the role of insulin in glucose uptake and its aberration in diabetes are well established, the effect of insulin on lipoprotein clearance in the postprandial phase is not yet fully understood...
  13. doi Role of insulin, insulin-like growth factor-1, hyperglycaemic food and milk consumption in the pathogenesis of acne vulgaris
    Bodo C Melnik
    Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabruck, Osnabruck, Germany
    Exp Dermatol 18:833-41. 2009
    It is the purpose of this viewpoint article to delineate the regulatory network of growth hormone (GH), insulin, and insulin-like growth factor-1 (IGF-1) signalling during puberty, associated hormonal changes in adrenal and gonadal ..
  14. doi In silico replication of the genome-wide association results of the Type 1 Diabetes Genetics Consortium
    Hui Qi Qu
    Department of Pediatrics, McGill University, Montreal, QC, Canada H4H 2P4
    Hum Mol Genet 19:2534-8. 2010
    ..This study replicated T1D association with at least as many of these novel loci as expected from the power of our sample size, thus supporting the validity of the new discoveries...
  15. pmc Investigation of type 1 diabetes and coeliac disease susceptibility loci for association with juvenile idiopathic arthritis
    Anne Hinks
    Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, Stopford Building, The University of Manchester, Manchester, UK
    Ann Rheum Dis 69:2169-72. 2010
    ..There is strong evidence suggesting that juvenile idiopathic arthritis (JIA) shares many susceptibility loci with other autoimmune diseases...
  16. ncbi Structure of a human insulin peptide-HLA-DQ8 complex and susceptibility to type 1 diabetes
    K H Lee
    Laboratory of Molecular Medicine, The Department of Medicine, The Children s Hospital, 320 Longwood Avenue, Boston, MA 02115, USA
    Nat Immunol 2:501-7. 2001
    ..we have determined the three-dimensional structure of DQ8 complexed with an immunodominant peptide from insulin. The similarity of the DQ8, DQ2 and I-A(g7) peptide-binding pockets suggests that diabetes is caused by the same ..
  17. ncbi Kinetics of different processes in human insulin amyloid formation
    Mauro Manno
    Institute of Biophysics at Palermo, Italian National Research Council, via U La Malfa 153, I 90146 Palermo, Italy
    J Mol Biol 366:258-74. 2007
    Human insulin has long been known to form amyloid fibrils under given conditions...
  18. pmc Two insulin gene single nucleotide polymorphisms associated with type 1 diabetes risk in the Finnish and Swedish populations
    Antti Pekka Laine
    Immunogenetics Laboratory, University of Turku, Turku, Finland
    Dis Markers 23:139-45. 2007
    We have developed high-throughput tests for the detection of the insulin gene region SNPs -23HphI and -2221MspI...
  19. ncbi The variable number of tandem repeats upstream of the insulin gene is a susceptibility locus for latent autoimmune diabetes in adults
    Minal Desai
    Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
    Diabetes 55:1890-4. 2006
    The etiopathological relationship between latent autoimmune diabetes in adults (LADA) and classical type 1 (insulin dependent) diabetes remains unclear...
  20. ncbi ATF-2 stimulates the human insulin promoter through the conserved CRE2 sequence
    Colin W Hay
    School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, AB25 2ZD, UK
    Biochim Biophys Acta 1769:79-91. 2007
    The insulin promoter contains a number of dissimilar cis-acting regulatory elements that bind a range of tissue specific and ubiquitous transcription factors...
  21. ncbi Amino-acid sequence of human insulin
    D S NICOL
    Nature 187:483-5. 1960
  22. ncbi Hormone-sensitive lipase has a role in lipid signaling for insulin secretion but is nonessential for the incretin action of glucagon-like peptide 1
    Marie Line Peyot
    Molecular Nutrition Unit, Department of Nutrition, University of Montréal and the Centre Hospitalier de l Université de Montréal, Montreal, Quebec, Canada
    Diabetes 53:1733-42. 2004
    We previously reported decreased glucose-stimulated insulin secretion (GSIS) in hormone-sensitive lipase-null mice (HSL(-/-)), both in vivo and in vitro...
  23. ncbi Heterogeneity in the magnitude of the insulin gene effect on HLA risk in type 1 diabetes
    Costantino Motzo
    Dipartimento di Scienze Biomediche e Biotecnologie, Universita di Cagliari, Sardinia, Italy
    Diabetes 53:3286-91. 2004
    ..products of the HLA and INS alleles, in which both the affinity of the various HLA class II molecules for a preproinsulin-derived peptide and the levels of this peptide in the thymus act jointly as key regulators of type 1 diabetes ..
  24. ncbi Effect of insulin with concurrent amino acid infusion on protein metabolism in rapidly growing pubertal children with type 1 diabetes
    Mushtaq A Godil
    Department of Pediatrics, State University of New York, Stony Brook, NY 11794, USA
    Pediatr Res 58:229-34. 2005
    b>Insulin treatment of prepubertal children with insulin-dependent diabetes improves body protein balance by decreasing the rate of protein degradation without stimulating protein synthesis...
  25. ncbi Genetic interaction among three genomic regions creates distinct contributions to early- and late-onset type 1 diabetes mellitus
    Eric I Felner
    Department of Pediatrics, Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, TX, USA
    Pediatr Diabetes 6:213-20. 2005
    ..antigen (HLA) complex (IDDM1); however, loci from the variable nucleotide tandem repeat (VNTR) region of the insulin (INS) gene (IDDM2) and more recently, the cytotoxic T-lymphocyte-associated protein-4 region (CTLA4, IDDM12) have ..
  26. ncbi Genetic association of type 1 diabetes in an Azerbaijanian population: the HLA-DQ, -DRB1*04, the insulin gene, and CTLA4
    Gunduz Ahmedov
    Azerbaijan Medical University, Str K Ragimov 11, Baku, Azerbaijan Republic
    Pediatr Diabetes 7:88-93. 2006
    ..Little is known on the genetic susceptibility to type 1 diabetes mellitus (T1DM) in the nations of the former Soviet part of south-west Asia...
  27. ncbi The neuronal Ca2+ sensor protein visinin-like protein-1 is expressed in pancreatic islets and regulates insulin secretion
    Feihan F Dai
    Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    J Biol Chem 281:21942-53. 2006
    ..knockdown by small interfering RNA caused a reduction in cAMP accumulation and produced a dramatic increase in preproinsulin mRNA, basal insulin secretion, and total cellular insulin content...
  28. ncbi Insulin controls subcellular localization and multisite phosphorylation of the phosphatidic acid phosphatase, lipin 1
    Thurl E Harris
    Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908 0735, USA
    J Biol Chem 282:277-86. 2007
    ..Fifteen phosphorylation sites were identified by mass spectrometric analyses. Insulin increased the phosphorylation of multiple sites and promoted a gel shift that was due in part to phosphorylation ..
  29. pmc Joint effects of HLA, INS, PTPN22 and CTLA4 genes on the risk of type 1 diabetes
    M Bjørnvold
    Institute of Medical Genetics, Faculty Division Ulleval University Hospital, University of Oslo, P O Box 1036, Blindern, NO 0315 Oslo, Norway
    Diabetologia 51:589-96. 2008
    ..Few studies have systematically investigated the joint effect of multiple genetic variants. We evaluated joint effects of the four established genes on the risk of childhood-onset type 1 diabetes...
  30. doi Association of type 1 diabetes with two Loci on 12q13 and 16p13 and the influence coexisting thyroid autoimmunity in Japanese
    Takuya Awata
    Division of Endocrinology and Diabetes, Department of Medicine, Saitama Medical University, 38 Morohongo, Moroyama, Iruma gun, Saitama 350 0495, Japan
    J Clin Endocrinol Metab 94:231-5. 2009
    ..Recent genome-wide association studies have identified several novel type 1 diabetes (T1D) loci in white populations...
  31. doi Effect of polymorphism in insulin locus and HLA on type 1 diabetes in four ethnic groups in Israel
    G Benedek
    The Lautenberg Center for General and Tumor Immunology, Hebrew University Hadassah Medical School, Jerusalem, Israel
    Tissue Antigens 73:33-8. 2009
    This study examined a possible association of the insulin (INS) gene with type 1 diabetes (T1D) in patients and controls from four ethnic groups in Israel...
  32. doi Single-nucleotide polymorphisms in the IL2RA gene are associated with age at diagnosis in late-onset Finnish type 1 diabetes subjects
    Matthew W Klinker
    Max McGee National Research Center for Juvenile Diabetes, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
    Immunogenetics 62:101-7. 2010
    ..These findings suggest that the IL2RA locus controls both the susceptibility to disease and its time of occurrence. Thus, we believe the IL2/IL2R axis represents a potential therapeutic target for delaying the onset of disease...
  33. pmc Posttranslational cleavage of proinsulin is blocked by a point mutation in familial hyperproinsulinemia
    Y Shibasaki
    J Clin Invest 76:378-80. 1985
    Familial hyperproinsulinemia is characterized by the accumulation of proinsulin-like material (PLM) in the plasma of affected patients. This disorder is inherited in an autosomal dominant fashion...
  34. ncbi Genetic variations within the insulin gene region are associated with accelerated fetal growth
    Hisao Osada
    Department of Obstetrics and Gynecology, Juntendo University Shizuoka Hospital, Shizuoka, Japan
    Tohoku J Exp Med 212:27-34. 2007
    ..to investigate the associations between the neonatal birth size and the genotypes of polymorphic loci within the insulin gene (INS) region, which is susceptible to diabetes mellitus...
  35. pmc Proinsulin maturation, misfolding, and proteotoxicity
    Ming Liu
    Division of Metabolism, Endocrinology, and Diabetes, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
    Proc Natl Acad Sci U S A 104:15841-6. 2007
    As a tool to explore proinsulin (PI) trafficking, a human PI cDNA has been constructed with GFP fused within the C peptide...
  36. doi Heterozygous missense mutations in the insulin gene are linked to permanent diabetes appearing in the neonatal period or in early infancy: a report from the French ND (Neonatal Diabetes) Study Group
    Michel Polak
    Faculty of Medicine, René Descartes Paris 5 University, Paris, France
    Diabetes 57:1115-9. 2008
    Permanent neonatal diabetes (PND) is defined by chronic hyperglycemia due to severe nonautoimmune insulin deficiency diagnosed in the first months of life...
  37. pmc Seven mutations in the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus
    Carlo Colombo
    Laboratory of Molecular Endocrinology and Metabolism, Bambino Gesu Children s Hospital, Scientific Institute and Department of Internal Medicine, University of Tor Vergata, Rome, Italy
    J Clin Invest 118:2148-56. 2008
    ..Similarly transfected INS-1E insulinoma cells had diminished viability compared with those expressing WT proinsulin. In conclusion, we find that mutations in the insulin gene that promote proinsulin misfolding may cause PNDM.
  38. pmc Diagnosis and treatment of neonatal diabetes: a United States experience
    Julie Støy
    Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
    Pediatr Diabetes 9:450-9. 2008
    ..The aim of this study was to identify the genetic cause of diabetes in 77 consecutive patients referred to the University of Chicago with diabetes diagnosed before 1 yr of age...
  39. ncbi Nucleotide sequence of a cDNA clone encoding human preproinsulin
    G I Bell
    Nature 282:525-7. 1979
  40. pmc Diabetes due to secretion of a structurally abnormal insulin (insulin Wakayama). Clinical and functional characteristics of [LeuA3] insulin
    K Nanjo
    J Clin Invest 77:514-9. 1986
    We have identified a non-insulin-dependent diabetic patient with fasting hyperinsulinemia (90 microU/ml), an elevated insulin:C-peptide molar ratio (1.68; normal, 0.05-0...
  41. pmc Localization of the human insulin gene to the distal end of the short arm of chromosome 11
    M E Harper
    Proc Natl Acad Sci U S A 78:4458-60. 1981
    The human insulin gene was mapped by hybridization in situ of 3H-labeled recombinant plasmid pHIG900 to chromosome preparations in the presence of 10% dextran sulfate...
  42. ncbi Class III alleles of the variable number of tandem repeat insulin polymorphism associated with silencing of thymic insulin predispose to type 1 diabetes
    P Vafiadis
    Endocrine Genetics Laboratory, McGill University Montreal Children s Hospital Research Institute, Quebec, Canada
    J Clin Endocrinol Metab 86:3705-10. 2001
    Type 1 diabetes results from autoimmune destruction of the insulin-producing pancreatic beta cells. The insulin gene (INS) is also expressed in human thymus, an ectopic expression site likely involved in immune tolerance...
  43. ncbi The mechanism of insulin action on islet amyloid polypeptide fiber formation
    Jennifer L Larson
    Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Avenue, New Haven, CT 06520 8114, USA
    J Mol Biol 335:221-31. 2004
    ..islet amyloid polypeptide (IAPP), is a hormone involved in glucose metabolism and is normally co-secreted with insulin by the beta-cells of the pancreas...
  44. pmc Proinsulin disulfide maturation and misfolding in the endoplasmic reticulum
    Ming Liu
    Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
    J Biol Chem 280:13209-12. 2005
    Upon nonreducing Tris-Tricine-urea-SDS-PAGE, newly synthesized proinsulin from pancreatic islets of normal rodents forms a band fast mobility representing the native disulfide isomer, which is efficiently secreted...
  45. pmc Glucose regulation of insulin gene transcription and pre-mRNA processing in human islets
    Carmella Evans-Molina
    University of Virginia Health System, 450 Ray C Hunt Drive, Charlottesville, VA 22908, USA
    Diabetes 56:827-35. 2007
    Glucose is the primary regulator of insulin granule release from pancreatic islets...
  46. ncbi Multiple factors affect the loss of measurable C-peptide over 6 years in newly diagnosed 15- to 35-year-old diabetic subjects
    Richard A Jensen
    Department of Biostatistics, University of Washington, Seattle, WA, USA
    J Diabetes Complications 21:205-13. 2007
    ..The aim of this study is to identify risk factors for the loss of measurable plasma C-peptide in newly diagnosed 15- to 35-year-old diabetic subjects...
  47. ncbi A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene
    Hakon Hakonarson
    Center for Applied Genomics, Abramson Research Center, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    Nature 448:591-4. 2007
    ..in children results from autoimmune destruction of pancreatic beta cells, leading to insufficient production of insulin. A number of genetic determinants of T1D have already been established through candidate gene studies, primarily ..
  48. pmc A novel point mutation in the human insulin gene giving rise to hyperproinsulinemia (proinsulin Kyoto)
    H Yano
    Department of Metabolism and Clinical Nutrition, Kyoto University Faculty of Medicine, Japan
    J Clin Invest 89:1902-7. 1992
    ..high performance liquid chromatography revealed a minor peak coeluting with human insulin and a major peak of proinsulin-like materials...
  49. ncbi Two unrelated patients with familial hyperproinsulinemia due to a mutation substituting histidine for arginine at position 65 in the proinsulin molecule: identification of the mutation by direct sequencing of genomic deoxyribonucleic acid amplified by pol
    F Barbetti
    Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892
    J Clin Endocrinol Metab 71:164-9. 1990
    ..Previously, two classes of mutations have been identified: 1) those that impair posttranslational processing of proinsulin to insulin, and 2) those that alter the structure of the insulin molecule, thereby reducing the affinity of the ..
  50. ncbi A genome-wide search for human type 1 diabetes susceptibility genes
    J L Davies
    Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Headington, UK
    Nature 371:130-6. 1994
    We have searched the human genome for genes that predispose to type 1 (insulin-dependent) diabetes mellitus using semi-automated fluorescence-based technology and linkage analysis...
  51. ncbi Susceptibility to insulin dependent diabetes mellitus maps to a 4.1 kb segment of DNA spanning the insulin gene and associated VNTR
    A M Lucassen
    Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK
    Nat Genet 4:305-10. 1993
    Recent studies have demonstrated that a locus at 11p15.5 confers susceptibility to insulin dependent diabetes mellitus (IDDM). This locus has been shown to lie within a 19 kb region...
  52. ncbi Insulin signalling and the regulation of glucose and lipid metabolism
    A R Saltiel
    Life Sciences Institute, Department of Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA
    Nature 414:799-806. 2001
    ..In both disorders, tissues such as muscle, fat and liver become less responsive or resistant to insulin. This state is also linked to other common health problems, such as obesity, polycystic ovarian disease, ..
  53. ncbi Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes
    Jinko Graham
    Department of Statistics and Actuarial Science, Simon Fraser University, Burnaby, Canada
    Diabetes 51:1346-55. 2002
    ..between type 1 diabetes risk genes HLA, INS VNTR, and CTLA-4 and autoantibodies to GAD65 (GADAs), ICA512/IA-2, insulin, and islet cells were determined by logistic regression analysis in 971 incident patients with type 1 diabetes ..
  54. ncbi Association of insulin gene VNTR polymorphism with polycystic ovary syndrome
    Marketa Vankova
    Institute of Endocrinology, Prague, Czech Republic
    Ann N Y Acad Sci 967:558-65. 2002
    Variability in the number of tandem repeats of the insulin gene (INS VNTR) is known to influence several phenotypes, including polycystic ovary syndrome (PCOS), diabetes mellitus type 1, diabetes mellitus type 2, and birth weight...
  55. ncbi Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved
    Giuseppe Pandini
    Istituto di Medicina Interna, Malattie Endocrine e del Metabolismo, University of Catania, Ospedale Garibaldi, 95123 Catania, Italy
    J Biol Chem 277:39684-95. 2002
    The insulin receptor (IR) and the insulin-like growth factor I receptor (IGF-IR) have a highly homologous structure, but different biological effects...
  56. pmc Polymorphism of the insulin gene is associated with increased prostate cancer risk
    G Y F Ho
    Department of Epidemiology and Social Medicine, Albert Eistein College of Medicine, Bronx, New York, NY 10461, USA
    Br J Cancer 88:263-9. 2003
    High insulin levels are linked with increased cancer risk, including prostate cancer...
  57. ncbi IDDM2/insulin VNTR modifies risk conferred by IDDM1/HLA for development of Type 1 diabetes and associated autoimmunity
    M Walter
    Diabetes Research Institute, Munich Schwabing Hospital, Kolner Platz 1, 80804 Munich, Germany
    Diabetologia 46:712-20. 2003
    ..The aim of this study was to determine whether combining IDDM1/HLA and IDDM2/ insulin( INS) 5' variable number of tandem repeat locus (VNTR) genotypes improves T1D risk assessment.
  58. ncbi Maternal-fetal interactions and birth order influence insulin variable number of tandem repeats allele class associations with head size at birth and childhood weight gain
    Ken K Ong
    Department of Pediatrics, University of Cambridge, Addenbrooke s Hospital, Cambridge, UK
    Diabetes 53:1128-33. 2004
    Polymorphism of the insulin gene (INS) variable number of tandem repeats (VNTR; class I or class III alleles) locus has been associated with adult diseases and with birth size...
  59. ncbi The effect of HLA class II, insulin and CTLA4 gene regions on the development of humoral beta cell autoimmunity
    Robert Hermann
    JDRF Centre for Prevention of Type 1 Diabetes in Finland, Turku, Finland
    Diabetologia 48:1766-75. 2005
    ..The aim of this study was to explore the contribution of genetic factors to the emergence of beta-cell-specific humoral autoimmunity...
  60. ncbi Insulin alleles and autoimmune regulator (AIRE) gene expression both influence insulin expression in the thymus
    Lidia Sabater
    Laboratory of Immunology for Research Applied to Diagnosis LIRAD, Blood and Tissue Bank, Institut d Investigació en Ciències de la Salut Germans Trias i Pujol, Hospital Universitari Germans Trias i Pujol, Crtra del Canyet s n, 08916 Badalona, Spain
    J Autoimmun 25:312-8. 2005
    It is well established that the polymorphisms at the 5' of the insulin gene (IDDM2) confers susceptibility to type 1 diabetes, probably by modifying the level of insulin expression in the thymus that in turn influences immunological ..
  61. ncbi Early events in the fibrillation of monomeric insulin
    Atta Ahmad
    Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA
    J Biol Chem 280:42669-75. 2005
    b>Insulin has a largely alpha-helical structure and exists as a mixture of hexameric, dimeric, and monomeric states in solution, depending on the conditions: the protein is monomeric in 20% acetic acid...
  62. ncbi Impact of IDDM2 on disease pathogenesis and progression in children with newly diagnosed type 1 diabetes: reduced insulin antibody titres and preserved beta cell function
    L B Nielsen
    Department of Paediatrics, Glostrup University Hospital, Ndr Ringvej 57, D 2600 Glostrup, Denmark
    Diabetologia 49:71-4. 2006
    The insulin-dependent diabetes mellitus 2 gene (IDDM2) is a type 1 diabetes susceptibility locus contributed to by the variable number of tandem repeats (VNTR) upstream of the insulin gene (INS)...
  63. ncbi Insulin control of placental gene expression shifts from mother to foetus over the course of pregnancy
    U Hiden
    Clinic of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz 14, 8036 Graz, Austria
    Diabetologia 49:123-31. 2006
    ..Both cell types produce high insulin receptor levels...
  64. ncbi Variants in the human insulin gene that affect pre-mRNA splicing: is -23HphI a functional single nucleotide polymorphism at IDDM2?
    Jana Kralovicova
    University of Southampton School of Medicine, Human Genetics Division, Duthie Building, MP808, Tremona Road, Southampton SO16 6YD, U K
    Diabetes 55:260-4. 2006
    ..We examined whether INS polymorphisms affect pre-mRNA splicing and proinsulin secretion using minigene reporter assays...
  65. ncbi Lymphoid tyrosine phosphatase (LYP/PTPN22) Arg620Trp variant regulates insulin autoimmunity and progression to type 1 diabetes
    R Hermann
    JDRF Centre for Prevention of Type 1 Diabetes in Finland, Turku, Finland
    Diabetologia 49:1198-208. 2006
    ..We also explored the heterogeneity in the disease-predisposing effect of this polymorphism in relation to known disease loci, sex and age at disease onset...
  66. ncbi The relation between size at birth and risk of type 1 diabetes is not influenced by adjustment for the insulin gene (-23HphI) polymorphism or HLA-DQ genotype
    L C Stene
    Division of Epidemiology, Norwegian Institute of Public Health, P O Box 4404, Nydalen, NO 0403, Oslo, Norway
    Diabetologia 49:2068-73. 2006
    Associations have been described between higher birthweight and increased risk of type 1 diabetes, and of insulin (INS) and human leucocyte antigen (HLA) genotypes that protect against diabetes with larger size at birth...
  67. ncbi Fibrillation of human insulin A and B chains
    Dong Pyo Hong
    Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA
    Biochemistry 45:9342-53. 2006
    Human insulin, which consists of disulfide cross-linked A and B polypeptide chains, readily forms amyloid fibrils under slightly destabilizing conditions...
  68. ncbi C-Peptide induces vascular smooth muscle cell proliferation: involvement of SRC-kinase, phosphatidylinositol 3-kinase, and extracellular signal-regulated kinase 1/2
    Daniel Walcher
    Department of Internal Medicine II, Cardiology, University of Ulm, Germany
    Circ Res 99:1181-7. 2006
    Increased levels of C-peptide, a cleavage product of proinsulin, circulate in patients with insulin resistance and early type 2 diabetes mellitus...
  69. ncbi The C-peptide fragment EVARQ reduces glomerular hyperfiltration in streptozotocin-induced diabetic rats
    Lina Nordquist
    Department of Medical Cell Biology, Division of Integrative Physiology, Uppsala University, Uppsala, Sweden
    Diabetes Metab Res Rev 23:400-5. 2007
    ..This study was designed to elucidate the effects of the C-peptide fragment EVARQ on kidney function, blood pressure and blood glucose levels in diabetic rats in vivo...
  70. ncbi The role of the IDDM2 locus in the susceptibility of UK APS1 subjects to type 1 diabetes mellitus
    K A Adamson
    Immunobiology Group, MRC Centre for Inflammation Research, University of Edinburgh, 47 Little France Crescent, Edinburgh, UK
    Int J Immunogenet 34:17-21. 2007
    ..However, alleles of a variable number tandem repeat (VNTR) 5' of the insulin gene are known to influence the development of T1D in the general, non-APS1 population...
  71. ncbi Evaluation of polymorphic splicing in the mechanism of the association of the insulin gene with diabetes
    Luc Marchand
    Endocrine Genetics Laboratory, McGill University Health Center, Montreal, Quebec, Canada H3H 1P3
    Diabetes 56:709-13. 2007
    The association of type 1 diabetes with the insulin gene (IDDM2 locus) has been mapped to a short haplotype encompassing two single nucleotide polymorphisms (SNPs) in perfect linkage disequilibrium (r(2) = 1) with each other and with the ..
  72. ncbi Insulin gene/IDDM2 locus in Japanese type 1 diabetes: contribution of class I alleles and influence of class I subdivision in susceptibility to type 1 diabetes
    Takuya Awata
    Division of Endocrinology and Diabetes, Department of Medicine, Saitama Medical University, 38 Morohongo, Moroyama, Iruma gun, Saitama 350 0495, Japan
    J Clin Endocrinol Metab 92:1791-5. 2007
    It is suggested that insulin autoimmunity plays an important role in the development of type 1 diabetes in humans. However, the association between insulin gene (INS) region (IDDM2) and type 1 diabetes has been uncertain in Asians.
  73. ncbi Human high-density lipoprotein particles prevent activation of the JNK pathway induced by human oxidised low-density lipoprotein particles in pancreatic beta cells
    A Abderrahmani
    Service of Internal Medicine, CHUV Hospital, Rue du Bugnon 9, 1005 Lausanne, Switzerland
    Diabetologia 50:1304-14. 2007
    ..We explored the potential adverse effects of pro-atherogenic oxidised LDL-cholesterol particles on beta cell function...
  74. pmc Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes
    John A Todd
    Juvenile Diabetes Research Foundation Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, University of Cambridge, Addenbrooke s Hospital, Cambridge CB2 0XY, UK
    Nat Genet 39:857-64. 2007
    ..Several regions, including 18q22 and 18p11, showed association with autoimmune thyroid disease. This study increases the number of T1D loci with compelling evidence from six to at least ten...
  75. 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
    ..The mutations are in critical regions of the preproinsulin molecule, and we predict that they prevent normal folding and progression of proinsulin in the insulin ..
  76. ncbi Activation of the insulin receptor by insulin and a synthetic peptide leads to divergent metabolic and mitogenic signaling and responses
    Maja Jensen
    Receptor Systems Biology Laboratory, Hagedorn Research Institute, 2820 Gentofte, Denmark
    J Biol Chem 282:35179-86. 2007
    Recently, single chain peptides have been designed that target the insulin receptor and mimic insulin action...
  77. ncbi Insulin gene variable number of tandem repeats is not associated with weight from fetal life until infancy: the Generation R Study
    Dennis O Mook-Kanamori
    The Generation R Study Group, Department of Epidemiology and Biostatistics, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands
    Eur J Endocrinol 157:741-8. 2007
    The aim of this study was to examine whether the insulin gene variable number of tandem repeats (INS VNTR) is associated with growth patterns in fetal life and infancy.
  78. doi Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes
    Anders Molven
    Gade Institute, University of Bergen, Norway
    Diabetes 57:1131-5. 2008
    Mutations in the insulin (INS) gene can cause neonatal diabetes. We hypothesized that mutations in INS could also cause maturity-onset diabetes of the young (MODY) and autoantibody-negative type 1 diabetes.
  79. pmc Insulin gene mutations as cause of diabetes in children negative for five type 1 diabetes autoantibodies
    Riccardo Bonfanti
    Department of Pediatrics, San Raffaele Hospital and Scientific Institute, Milan, Italy
    Diabetes Care 32:123-5. 2009
    Heterozygous, gain-of-function mutations of the insulin gene can cause permanent diabetes with onset ranging from the neonatal period through adulthood...
  80. pmc Cx36 makes channels coupling human pancreatic beta-cells, and correlates with insulin expression
    Veronique Serre-Beinier
    Surgical Research Unit, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland
    Hum Mol Genet 18:428-39. 2009
    Previous studies have documented that the insulin-producing beta-cells of laboratory rodents are coupled by gap junction channels made solely of the connexin36 (Cx36) protein, and have shown that loss of this protein desynchronizes beta-..
  81. pmc Shared and distinct genetic variants in type 1 diabetes and celiac disease
    Deborah J Smyth
    Juvenile Diabetes Research Foundation Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke s Hospital, Cambridge, United Kingdom
    N Engl J Med 359:2767-77. 2008
    ..Since both diseases are associated with the HLA class II genes on chromosome 6p21, we tested whether non-HLA loci are shared...
  82. pmc Do non-HLA genes influence development of persistent islet autoimmunity and type 1 diabetes in children with high-risk HLA-DR,DQ genotypes?
    Andrea K Steck
    Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado, USA
    Diabetes 58:1028-33. 2009
    ..We examined whether some of these alleles influence development of islet autoimmunity or progression from persistent islet autoimmunity to type 1 diabetes in children with high-risk HLA-DR,DQ genotypes...
  83. pmc Insulin gene expression is regulated by DNA methylation
    Akio Kuroda
    Department of Diabetes, Endocrinology, and Metabolism, Research Institute of City of Hope, Duarte, California, United States of America
    PLoS ONE 4:e6953. 2009
    b>Insulin is a critical component of metabolic control, and as such, insulin gene expression has been the focus of extensive study...
  84. pmc Insulin gene mutations resulting in early-onset diabetes: marked differences in clinical presentation, metabolic status, and pathogenic effect through endoplasmic reticulum retention
    Gargi Meur
    Section of Cell Biology, Division of Medicine, Imperial College London, London, UK
    Diabetes 59:653-61. 2010
    Heterozygous mutations in the human preproinsulin (INS) gene are a cause of nonsyndromic neonatal or early-infancy diabetes...
  85. pmc Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism
    Mathieu Ferron
    Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Cell 142:296-308. 2010
    The broad expression of the insulin receptor suggests that the spectrum of insulin function has not been fully described...
  86. pmc Proinsulin misfolding and diabetes: mutant INS gene-induced diabetes of youth
    Ming Liu
    Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical Center, Ann Arbor, MI, USA
    Trends Endocrinol Metab 21:652-9. 2010
    ..dominant Mutant INS-gene Induced Diabetes of Youth (MIDY) syndrome, but most missense mutations affecting proinsulin folding produce MIDY...
  87. pmc Arp2/3- and cofilin-coordinated actin dynamics is required for insulin-mediated GLUT4 translocation to the surface of muscle cells
    Tim Ting Chiu
    Program in Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada
    Mol Biol Cell 21:3529-39. 2010
    GLUT4 vesicles are actively recruited to the muscle cell surface upon insulin stimulation...
  88. pmc Clinical and molecular genetics of neonatal diabetes due to mutations in the insulin gene
    Julie Støy
    Department of Internal Medicine and Endocrinology, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark
    Rev Endocr Metab Disord 11:205-15. 2010
    ..Recently, mutations in the insulin gene (INS) itself have been identified as another cause of neonatal diabetes...
  89. ncbi The human leukocyte antigen genotype has a modest effect on the insulin gene polymorphism-associated susceptibility to type 1 diabetes in the Finnish population
    A P Laine
    JDRF Centre for Prevention of Type 1 Diabetes, Department of Virology, University of Turku, Turku, Finland
    Tissue Antigens 63:72-4. 2004
    In addition to the known human leukocyte antigen (HLA)-associated risk, polymorphisms of insulin gene region show association with type 1 diabetes...
  90. ncbi Analysis of multiple data sets reveals no association between the insulin gene variable number tandem repeat element and polycystic ovary syndrome or related traits
    Brenda L Powell
    Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom
    J Clin Endocrinol Metab 90:2988-93. 2005
    Variation at the insulin gene VNTR (variable number tandem repeat) minisatellite has been reported to be associated with polycystic ovary syndrome (PCOS), but findings have been inconsistent and all studies have featured small sample ..
  91. ncbi Insulin gene polymorphism in women with polycystic ovary syndrome
    P Ferk
    Faculty of Medicine, University of Maribor, Maribor, Slovenia
    J Int Med Res 36:1180-7. 2008
    b>Insulin resistance is one of the main characteristics of polycystic ovary syndrome (PCOS) and is probably genetically predisposed...
  92. ncbi Studies on human proinsulin. Isolation and amino acid sequence of the human pancreatic C-peptide
    P E Oyer
    J Biol Chem 246:1375-86. 1971
  93. ncbi Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus
    S T Bennett
    Nuffield Department of Surgery, Wellcome Trust Centre for Human Genetics, University of Oxford, UK
    Nat Genet 9:284-92. 1995
    The IDDM2 locus encoding susceptibility to type 1 diabetes was mapped previously to a 4.1-kb region spanning the insulin gene and a minisatellite or variable number of tandem repeats (VNTR) locus on human chromosome 11p15.5...
  94. pmc Structural analysis of insulin minisatellite alleles reveals unusually large differences in diversity between Africans and non-Africans
    John D H Stead
    Department of Genetics, University of Leicester, United Kingdom
    Am J Hum Genet 71:1273-84. 2002
    The insulin minisatellite (INS VNTR) associates with susceptibility to a variety of diseases...
  95. ncbi Variation at the insulin gene VNTR (variable number tandem repeat) polymorphism and early growth: studies in a large Finnish birth cohort
    Amanda J Bennett
    Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Headington, Oxford, UK
    Diabetes 53:2126-31. 2004
    Variation at the insulin gene (INS-)VNTR (variable number of tandem repeats) minisatellite polymorphism has been reported to be associated with both early growth and adult metabolic phenotypes...
  96. ncbi Association between small for gestational age and paternally inherited 5' insulin haplotypes
    R M Adkins
    Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USA
    Int J Obes (Lond) 32:372-80. 2008
    To test the association between small for gestational age and polymorphisms in the insulin gene in newborns and their mothers, as well as the effect of the parental transmission of haplotypes.
  97. pmc Permanent diabetes during the first year of life: multiple gene screening in 54 patients
    L Russo
    Laboratory of Mendelian Diabetes, Ospedale Pediatrico Bambino Gesu, IRCCS, Rome, Italy
    Diabetologia 54:1693-701. 2011
    ..The aim of this study was to investigate the genetic aetiology of permanent diabetes mellitus with onset in the first 12 months of age...
  98. pmc Identification of a mutant human insulin predicted to contain a serine-for-phenylalanine substitution
    S Shoelson
    Proc Natl Acad Sci U S A 80:7390-4. 1983
    Using information gained from (i) the relative HPLC retention of an abnormal insulin present in the serum of a hyperinsulinemic diabetic patient and (ii) the loss of an Mbo II restriction site in one of the patient's insulin gene alleles,..
  99. ncbi Systematic search for single nucleotide polymorphisms in the insulin gene: evidence for a high frequency of -23T-->A in Japanese subjects
    H Osawa
    Department of Laboratory Medicine, Ehime University School of Medicine, Shigenobu, Ehime, 791 0295, Japan
    Biochem Biophys Res Commun 286:451-5. 2001
    It has recently been shown that the A/A genotype at g.-23 of the insulin gene correlates with impaired insulin secretion in response to body weight gain in subjects of European descent...
  100. ncbi 5'-Insulin gene VNTR polymorphism is specific for type 1 diabetes: no association with celiac or Addison's disease
    Guiomar Perez de Nanclares
    Endocrinology and Diabetes Research Unit, Hospital de Cruces, Barakaldo, Basque Country, Spain
    Ann N Y Acad Sci 1005:319-23. 2003
    The VNTR region located at the 5'-end of the insulin gene on chromosome 11p15...

Research Grants62

  1. Randal J Kaufman; Fiscal Year: 2014
    ..Aim 2, What is the relationship between protein folding and oxidative stress? We will evaluate proinsulin folding and processing and mitochondrial function in these studies...
  2. Randal J Kaufman; Fiscal Year: 2016
    ..3) IRE1a-mediated splicing of Xbp1 mRNA induces co-transiational translocation at the ER to promote proinsulin production and represses oxidative stress...
  3. Douglas R Cavener; Fiscal Year: 2016
    ..The focus of this proposal is to investigate the role of the PERK eIF2a kinase (EIF2AK3) in regulating proinsulin trafficking and quality control in the endoplasmic reticulum...
  4. Peter Arvan; Fiscal Year: 2016
    ..Insulin synthesis begins with translation of preproinsulin for delivery into the lumen of the endoplasmic reticulum (ER)...
  5. Low-cost proinsulin-transferrin fusion protein in rice for treatment of diabetes
    Deshui Zhang; Fiscal Year: 2013
    ..A recombinant proinsulin-transferrin (ProINS-Tf) fusion protein was recently found to facilitate an enhanced and sustained in vivo ..
  6. JAMES RUSSELL SOWERS; Fiscal Year: 2015
    DESCRIPTION (provided by applicant): Diminished insulin (INS) sensitivity is a common feature of disease states such as obesity, hypertension and diabetes...
  7. ENGINEERED GLUCOSE METABOLISM IN INSULIN SECRETING CELLS
    Christopher B Newgard; Fiscal Year: 2010
    ..the pyruvate cycling enzymes ICDc and MEc controls expression of neuroendocrine protein 7B2, a regulator of the proinsulin processing enzyme PC2, thereby affecting proinsulin:insulin ratios;4) To translate information about new targets ..
  8. Christopher J Rhodes; Fiscal Year: 2014
    ..translational regulation is guided by conserved cis-elements that reside in the untranslated regions (UTRs) of preproinsulin mRNA (PPI mRNA)...
  9. METABOLIC CONTROL OF PROINSULIN BIOSYNTHESIS TRANSLATION
    Christopher Rhodes; Fiscal Year: 2009
    ..translational regulation is guided by conserved cis-elements that reside in the untranslated regions (UTRs) of preproinsulin mRNA (PPI mRNA)...
  10. Rohit N Kulkarni; Fiscal Year: 2016
    ..continue our studies with the following Specific Aims: Aim 1: Determine the role of insulin/IGF-I signaling in proinsulin processing and test the hypothesis that an intact insulin/IRS-2 pathway is essential for appropriate proinsulin ..
  11. Role of IGF-1 and insulin receptors beta-cell survival
    Rohit N Kulkarni; Fiscal Year: 2010
    ..continue our studies with the following Specific Aims: Aim 1: Determine the role of insulin/IGF-I signaling in proinsulin processing and test the hypothesis that an intact insulin/IRS-2 pathway is essential for appropriate proinsulin ..
  12. MICHAEL AARON WEISS; Fiscal Year: 2014
    DESCRIPTION (provided by applicant): How mutations in proinsulin cause diabetes: a protein-misfolding disease Insulin plays a central role in the regulation of vertebrate metabolism...
  13. Alteration in protein interactions with proinsulin and insulin in type 2 diabetes
    Randal J Kaufman; Fiscal Year: 2011
    ..by applicant): Type 2 diabetes (T2D) is disease epidemic caused by a failure of beta cells to produce sufficient insulin to maintain euglycemia...
  14. Ming Liu; Fiscal Year: 2015
    ..In ?-cells, insulin synthesis begins with the precursor, preproinsulin, which must undergo co-translational translocation into the endoplasmic reticulum (ER), signal peptide (SP) ..
  15. Peter A Gottlieb; Fiscal Year: 2016
    ..Specific Aims: 1) BHT-3021 Proinsulin DNA vaccine treatment of recent onset type 1 diabetes subjects Research Design: Preliminary data in animals has ..
  16. Zinc Transporter-8-Specific T Cell Responses in the Prediction of Type 1 Diabetes
    HELENA KRISTIINA REIJONEN; Fiscal Year: 2013
    ..we will test the hypothesis that polymorphism in the SLC30A8 gene has an effect on the T cell responses to proinsulin through altered proinsulin processing, which has been reported to be associated with this genomic variant...
  17. Training-Muscle Blood Flow and Capillary Dynamics
    M Harold Laughlin; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): We will test the hypothesis that: exercise training (EX) improves insulin (INS) sensitivity in type 2 diabetes (T2D), in part, by adaptations that improve skeletal muscle (skmus) blood flow (BF) via ..
  18. L-type Ca2+ Channel Modulation of Beta Cell Function
    GREGORY HOWARD HOCKERMAN; Fiscal Year: 2012
    Project Summary In type II diabetes, the insulin secreting beta cells of pancreatic islets fail to secrete insulin in sufficient quantities to maintain normal blood glucose levels...
  19. Wei Chiang Shen; Fiscal Year: 2014
    ..e., granulocyte colony-stimulating factor (G-CSF), human growth hormone (hGH) and proinsulin (ProINS)...
  20. JORDAN JAMES WRIGHT; Fiscal Year: 2014
    ..In beta cells, proinsulin synthesis can account for up to 50% of total protein synthesized by the cell, so even fractional proinsulin ..
  21. Analysis of diabetogenic human T cell receptors
    Howard W Davidson; Fiscal Year: 2011
    ..of autoimmunity, which will likely result in those persons having a larger precursor pool of ZnT8-specific than proinsulin-specific na[unreadable]ve T-cells that can be induced to adopt an immunoregulatory phenotype at the onset of ..
  22. Marian J Rewers; Fiscal Year: 2016
    ..We believe our MSD insulin autoantibody assay utilizing proinsulin can be improved but even with its current performance will likely replace fluid phase insulin autoantibody ..
  23. Teresa P DiLorenzo; Fiscal Year: 2015
    ..Using a reagent that we have recently produced, we propose to deliver the beta cell antigen proinsulin to DC and determine the effect of this treatment on pathogenic CD8+ and CD4+ T cells and on the induction of ..
  24. ROBERT ARTHUR CHONG; Fiscal Year: 2015
    ..Therefore, I plan to use viral vectors to deliver islet-specific antigens (Proinsulin and GAD65) to non-activated DCs, and restrict their expression in activated ones by incorporating target sites ..
  25. CHEMICAL AND STRUCTURAL SIGNATURES OF INSULIN FUNCTION
    Michael Dunn; Fiscal Year: 1992
    ..of this project is to further our knowledge of structure-function interrelationships for human insulin and proinsulin. The specific objectives are to answer the following questions: (a) How different are the solution structures of ..
  26. Beta-cell Compensation in Partial Pancreatectomy Mice
    JOHN L LEAHY; Fiscal Year: 2013
    ..Changes in insulin sensitivity and/or [unreadable]-cell mass elicit precise adaptations from the remaining [unreadable]-cells so ..
  27. Virginia H Huxley; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): Prior to diagnosis of type 2 diabetes (DM2) the state of insulin resistance (InsR) exists...
  28. Autophagy and human islet amyloid polypeptide in animal models of type 2 diabetes
    Jacqueline Rivera; Fiscal Year: 2013
    ..There is an increasing appreciation that the underlying mechanism leading to T2DM is inadequate insulin secretion in response to insulin resistance, the latter most commonly secondary to a lifestyle with high calorie ..
  29. JAMES RUSSELL SOWERS; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): Project Summary/Abstract Impaired insulin (INS) sensitivity is a common feature of disease states such as obesity, hypertension and diabetes...
  30. ERR-gamma-dependent mammary tumorigenesis in response to BPA and a high-fat diet
    Rebecca B Riggins; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Diet-induced obesity, insulin (INS) resistance, and type 2 diabetes have reached epidemic proportion among women in the United States, and each of these health problems significantly increase a woman&..
  31. Mechanisms of Islet Beta Cell Dysfunction in Diabetes
    Anjaneyulu Kowluru; Fiscal Year: 2013
    ..CER-dependent signaling mechanisms might underlie -cell dysfunction in in vitro and in vivo models of impaired insulin secretion, very little is known with regard to the precise modes of action of CER in the signaling events leading ..
  32. Paradoxical Roles of Reactive Oxygen Species in Pancreatic Beta-Cell Function
    Jingbo Pi; Fiscal Year: 2009
    ..Project Summary: Impaired metabolic signal transduction that mediates insulin secretion is fundamental in the pathophysiology of diabetes...
  33. Laura C Alonso; Fiscal Year: 2016
    ..People with diabetes have reduced beta cell mass;developing therapies that increase beta cell mass, to increase insulin secretory capacity, is a primary goal in diabetes research...
  34. Neuroligins and Neuroligin-Neurexin Interactions in Islet Beta Cell Function
    Steven D Chessler; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The development of glucose-responsive, insulin-secreting cells for beta cell replacement therapy will require a better understanding of the molecular determinants of pancreatic islet function and ..
  35. Targeting crosstalk between insulin and Gq signaling systems in pancreatic cancer
    JUAN ENRIQUE ROZENGURT; Fiscal Year: 2010
    ..pancreas, a unique feature of the pancreatic microenvironment is the potential influence of locally produced insulin on pancreatic cancer cell development...
  36. Reversal of Autoimmune Diabetes
    Habib Zaghouani; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Type I diabetes (T1D) is a spontaneous autoimmune disease in which the insulin-producing [unreadable] cells of the pancreatic islets are destroyed as a consequence of immune inflammatory reactions...
  37. POST-TRANSCRIPTIONAL CONTROL OF PROINSULIN SYNTHESIS
    JOSE CIMADEVILLA; Fiscal Year: 1980
    The initial, preferential stimulation of proinsulin synthesis in isolated islets of Langerhans by glucose appears to involve certain elements of posttranscriptional control...
  38. Lawrence Chan; Fiscal Year: 2014
    ..We recently found that diabetes is associated with the appearance of proinsulin-positive cells in the bone marrow (Kojima et al., 2004)...
  39. Lakshmidevi Pulakat; Fiscal Year: 2016
    ..b>Insulin (INS) resistance that underlies MetS exacerbates vascular complications, cardiovascular remodeling, and CVD ..
  40. Anath Shalev; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): Loss of functional beta cell mass by beta cell apoptosis and inadequate insulin production is a hallmark of type 1 and type 2 diabetes...
  41. School Nurse Intervention and After School Exercise Program for Overweight Teens
    Lori Pbert; Fiscal Year: 2012
    ..sedentary behavior) and on secondary physiologic (waist circumference, body fat, blood pressure, lipids, and insulin sensitivity) and psychosocial (e.g., self-efficacy, quality of life, and depression) outcomes...
  42. Hybridization of Promoter DNA Targets in Chromatin to Discover Regulatory Protein
    LINDA B MC GOWN; Fiscal Year: 2010
    ..chromatin antisense rehybridization (CAR) and chromatin sense rehybridization (CSR) with the model system of the insulin- linked polymorphic region (ILPR), and (2) evaluate the effectiveness of CAR and CSR to probe the proteins ..
  43. Phosphoinositide Phosphatases
    Jack E Dixon; Fiscal Year: 2013
    ..Second, we have demonstrated that PTPMT1 regulates insulin secretion by decreasing ATP production in INS-1 cells...
  44. Paolo Serafini; Fiscal Year: 2014
    ..and it is still unknown which one (if any) is the most "important" one, accumulating evidence suggests that insulin is a key target of pathogenic T cells in type 1 diabetes in both NOD mice and humans, and that it may even be the ..
  45. DARIO AA VIGNALI; Fiscal Year: 2014
    ..is a complex disease that is mediated by T cell entry into pancreatic islets and the subsequent destruction of insulin-producing b cells...
  46. EMIL RAPHAEL UNANUE; Fiscal Year: 2016
    ..It is based on recent progress that led to the identification of insulin (INS) as a major autoantigen...
  47. Effect of G-rich Higher Order Structures on Insulin Linked Polymorphism Region
    Hanbin Mao; Fiscal Year: 2010
    ..aims to improve the health and well-being of Americans with disorders that have hereditary components, such as Insulin Dependent Diabetes Mellitus (IDDM, type I diabetes), fragile X syndrome and Huntington's disease, by ..
  48. Achieving Therapeutic Antigent-Specific Tolerance in Type 1 Diabetes
    Matthias G Von Herrath; Fiscal Year: 2011
    ..therapeutic regimen in recent-onset T1D in vivo? Current data indicate that oral or nasal administration of insulin peptides bears most promise...
  49. A Humanized mouse model of B-islet cell autoimmunity
    Grete Sonderstrup; Fiscal Year: 2010
    ..in both HLA- DR*0401 transgenic mice and HLA-DR*0401 positive T1D patients, a correctly expressed human preproinsulin transgene (hu-PPI) is also being added...
  50. VACCINIA VIRUS VACCINE FOR TYPE 1 DIABETES
    William Langridge; Fiscal Year: 2003
    ..Genes encoding proinsulin (INS) and glutamate decarboxylase (GAD) autoantigens fused to a cholera toxin B subunit (CTB) receptor IJgand in ..
  51. PROCESSING OF PROINSULIN/INSULIN BY B-CELL ORGANELLES
    Philippe Halban; Fiscal Year: 1993
    ..The specific aims for the next 3 Year Period are: 1. How is proinsulin transported from the RER to the cis-Golgi? The effects of inhibitors on localization (immunocytochemistry) and ..
  52. Autoantigen delivery to induce tolerance in diabetic ra*
    William Osborne; Fiscal Year: 2002
    ..This research will test the hypothesis that constitutive expression of secretable GAD65 or proinsulin will tolerize diabetes prone rats and prevent or significantly delay the onset of diabetes...
  53. GENETIC EPIDEMIOLOGY OF NIDDM IN MEXICAN AMERICANS
    Michael Stern; Fiscal Year: 2000
    ..for linkage to the following traits: diabetes, fasting and 2-hour glucose, fasting and 2-hour insulin, fasting proinsulin, fasting proinsulin split products, and a panel of anthropometric measures...
  54. PROINSULIN EXPRESSION IN THE IMMUNE SYSTEM
    Alberto Pugliese; Fiscal Year: 2000
    ..gene (INS) is naturally transcribed in the human thymus and that thymic INS transcription correlates with proinsulin synthesis...
  55. IFN GAMMA-TREATED PANCREATIC BETA-CELLS
    H Gaskins; Fiscal Year: 1999
    ..hypothesis is that intracellular insulin content is diminished in IFNgamma-treated beta-cells because pre-proinsulin is diverted from the normal secretory pathway and used as a donor of antigenic peptides for MHC class I assembly...
  56. Signal Transduction Leading to Insulin Synthesis
    Gene Webb; Fiscal Year: 2007
    ..of beta cells induces specific signal-transduction pathways that differentially regulate the translation of proinsulin. These mechanisms may contribute to the development of type 2 diabetes...
  57. HUMAN NEUROENDOCRINE CELL LINES FOR DIABETES THERAPY
    HANS HOHMEIER; Fiscal Year: 2000
    ..origin for this purpose, based on encouraging preliminary data showing complete processing of expressed proinsulin in such cells...
  58. Analysis of beta cell death in Type 1 diabetes
    Kevan C Herold; Fiscal Year: 2013
    ..They may develop new treatment strategies based on an improved understanding of the kinetics and mechanisms of disease pathogenesis. ..
  59. Systems Genetics of Type 1 Diabetes Complications
    Aldons Jake Lusis; Fiscal Year: 2011
    ..The goal of this project, identifying molecular mechanisms responsible for diabetes accelerated diseases, remains a critical goal in the drive to develop better treatments and preventative measures. ..
  60. Epigenetic Status of MAOA Gene as a Module of Translational Behavioral Research
    Elena Shumay; Fiscal Year: 2013
    ..abstract_text> ..
  61. The Function of Phospholipase A2 in Islet Beta-cells
    Zhongmin Ma; Fiscal Year: 2007
    Defective or abnormal insulin secretion by islets in response to glucose results in diabetes mellitus (DM)...
  62. Keith T Wilson; Fiscal Year: 2014
    ..The studies proposed seek new strategies for amelioration or prevention of H. pylori-induced disease by clarifying targets for intervention in the pathogenic immune response that lead to disease persistence and cancer risk. ..