islets of langerhans

Summary

Summary: Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.

Top Publications

  1. ncbi Mechanisms linking obesity to insulin resistance and type 2 diabetes
    Steven E Kahn
    Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, 1660 South Columbian Way, Seattle, Washington 98108, USA
    Nature 444:840-6. 2006
  2. ncbi Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes
    Alexandra E Butler
    Division of Endocrinology and Diabetes, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    Diabetes 52:102-10. 2003
  3. ncbi Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells
    Kevin A D'Amour
    Novocell Inc, 3550 General Atomics Ct, San Diego, California 92121, USA
    Nat Biotechnol 24:1392-401. 2006
  4. doi The role of inflammation in insulitis and beta-cell loss in type 1 diabetes
    Decio L Eizirik
    Laboratory of Experimental Medicine, Medical Faculty, Universite Libre de Bruxelles, 808 Route de Lennik, Brussels, Belgium
    Nat Rev Endocrinol 5:219-26. 2009
  5. pmc The unique cytoarchitecture of human pancreatic islets has implications for islet cell function
    Over Cabrera
    Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
    Proc Natl Acad Sci U S A 103:2334-9. 2006
  6. pmc A gene expression network model of type 2 diabetes links cell cycle regulation in islets with diabetes susceptibility
    Mark P Keller
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53076, USA
    Genome Res 18:706-16. 2008
  7. pmc miR-375 maintains normal pancreatic alpha- and beta-cell mass
    Matthew N Poy
    Institute of Molecular Systems Biology, Swiss Federal Institute of Technology, ETH Zurich, CH 8093 Zurich, Switzerland
    Proc Natl Acad Sci U S A 106:5813-8. 2009
  8. ncbi Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats
    G Xu
    Elliott P Joslin Research Laboratories, Joslin Diabetes Center, Boston, Massachusetts 02215, USA
    Diabetes 48:2270-6. 1999
  9. ncbi Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes
    R Paul Robertson
    Pacific Northwest Research Institute and the Departments of Medicine and Pharmacology, University of Washington, Seattle, Washington 98122, USA
    Diabetes 53:S119-24. 2004
  10. ncbi Insulin granule dynamics in pancreatic beta cells
    P Rorsman
    The Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Headington, Oxford, UK
    Diabetologia 46:1029-45. 2003

Detail Information

Publications279 found, 100 shown here

  1. ncbi Mechanisms linking obesity to insulin resistance and type 2 diabetes
    Steven E Kahn
    Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, 1660 South Columbian Way, Seattle, Washington 98108, USA
    Nature 444:840-6. 2006
    ..This knowledge is fostering exploration of the molecular and genetic basis of the disease and new approaches to its treatment and prevention...
  2. ncbi Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes
    Alexandra E Butler
    Division of Endocrinology and Diabetes, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    Diabetes 52:102-10. 2003
    ....
  3. ncbi Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells
    Kevin A D'Amour
    Novocell Inc, 3550 General Atomics Ct, San Diego, California 92121, USA
    Nat Biotechnol 24:1392-401. 2006
    ..Production of these hES cell-derived endocrine cells may represent a critical step in the development of a renewable source of cells for diabetes cell therapy...
  4. doi The role of inflammation in insulitis and beta-cell loss in type 1 diabetes
    Decio L Eizirik
    Laboratory of Experimental Medicine, Medical Faculty, Universite Libre de Bruxelles, 808 Route de Lennik, Brussels, Belgium
    Nat Rev Endocrinol 5:219-26. 2009
    ..These stages, and their progression or resolution, might depend on a patient's genetic background, which contributes to disease heterogeneity...
  5. pmc The unique cytoarchitecture of human pancreatic islets has implications for islet cell function
    Over Cabrera
    Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
    Proc Natl Acad Sci U S A 103:2334-9. 2006
    ..We conclude that the unique cellular arrangement of human islets has functional implications for islet cell function...
  6. pmc A gene expression network model of type 2 diabetes links cell cycle regulation in islets with diabetes susceptibility
    Mark P Keller
    Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53076, USA
    Genome Res 18:706-16. 2008
    ....
  7. pmc miR-375 maintains normal pancreatic alpha- and beta-cell mass
    Matthew N Poy
    Institute of Molecular Systems Biology, Swiss Federal Institute of Technology, ETH Zurich, CH 8093 Zurich, Switzerland
    Proc Natl Acad Sci U S A 106:5813-8. 2009
    ..These data provide evidence that miR-375 is essential for normal glucose homeostasis, alpha- and beta-cell turnover, and adaptive beta-cell expansion in response to increasing insulin demand in insulin resistance...
  8. ncbi Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats
    G Xu
    Elliott P Joslin Research Laboratories, Joslin Diabetes Center, Boston, Massachusetts 02215, USA
    Diabetes 48:2270-6. 1999
    ..Thus, GLP-I and analogs thereof hold promise as a novel therapy to stimulate beta-cell growth and differentiation when administered to diabetic individuals with reduced beta-cell mass...
  9. ncbi Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes
    R Paul Robertson
    Pacific Northwest Research Institute and the Departments of Medicine and Pharmacology, University of Washington, Seattle, Washington 98122, USA
    Diabetes 53:S119-24. 2004
    ....
  10. ncbi Insulin granule dynamics in pancreatic beta cells
    P Rorsman
    The Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Headington, Oxford, UK
    Diabetologia 46:1029-45. 2003
    ..Here we discuss these observations in relation to previous functional and ultra-structural data as well as the secretory defects of Type 2 diabetes...
  11. pmc Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GIP- and GLP-1 receptors and impaired beta-cell function
    Luan Shu
    Islet Biology Laboratory, Centre for Biomolecular Interactions Bremen, University of Bremen, Bremen, Germany
    Hum Mol Genet 18:2388-99. 2009
    ..Our findings suggest that beta-cell function and survival are regulated through an interplay between TCF7L2 and GLP-1R/GIP-R expression and signaling in T2DM...
  12. ncbi Five stages of evolving beta-cell dysfunction during progression to diabetes
    Gordon C Weir
    Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA
    Diabetes 53:S16-21. 2004
    ..For type 1 diabetes, as remission develops, progression from stage 4 to stage 2 is typically found. Delineation of these stages provides insight into the pathophysiology of both progression and remission of diabetes...
  13. ncbi Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes
    R Paul Robertson
    Pacific Northwest Research Institute, Seattle, Washington 98122, USA
    J Biol Chem 279:42351-4. 2004
  14. ncbi Disruption of IRS-2 causes type 2 diabetes in mice
    D J Withers
    Howard Hughes Medical Institute, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Nature 391:900-4. 1998
    ..Our results indicate that dysfunction of IRS-2 may contribute to the pathophysiology of human type 2 diabetes...
  15. doi Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet
    Chie Ebato
    Department of Medicine, Endocrinology, and Metabolism, Juntendo University School of Medicine, 2 1 1 Hongo, Bunkyo ku, Tokyo 113 8421, Japan
    Cell Metab 8:325-32. 2008
    ..The results also identified a unique role for inductive autophagy as an adaptive response of beta cells in the presence of insulin resistance induced by high-fat diet...
  16. pmc Rapid insulinotropic action of low doses of bisphenol-A on mouse and human islets of Langerhans: role of estrogen receptor β
    Sergi Soriano
    Instituto Bioingeniería and CIBER de Diabetes y Enfermedades Metabólicas Asociadas, Universidad Miguel Hernandez de Elche, Elche, Alicante, Spain
    PLoS ONE 7:e31109. 2012
    ..We also investigated these effects of BPA in β-cells and whole islets of Langerhans from humans...
  17. ncbi Mitochondrial function in normal and diabetic beta-cells
    P Maechler
    Division of Clinical Biochemistry, Department of Internal Medicine, University Medical Centre, 1211 Geneva 4, Switzerland
    Nature 414:807-12. 2001
    ..The latter process requires an increase in cytosolic Ca2+, which depends on ATP synthesized by the mitochondria. This organelle also generates other factors, of which glutamate has been proposed as a potential intracellular messenger...
  18. pmc The estrogenic effect of bisphenol A disrupts pancreatic beta-cell function in vivo and induces insulin resistance
    Paloma Alonso-Magdalena
    Instituto de Bioingenieria, Universidad Miguel Hernandez de Elche, Alicante, Spain
    Environ Health Perspect 114:106-12. 2006
    ..Therefore, either abnormal levels of endogenous estrogens or environmental estrogen exposure enhances the risk of developing type 2 diabetes mellitus, hypertension, and dyslipidemia...
  19. pmc Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion
    C Ling
    Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, CRC, 205 02 Malmo, Sweden
    Diabetologia 51:615-22. 2008
    ..We also tested if experimental downregulation of PPARGC1A expression in human islets influenced insulin secretion...
  20. ncbi Chronic palmitate but not oleate exposure induces endoplasmic reticulum stress, which may contribute to INS-1 pancreatic beta-cell apoptosis
    Elizabeth Karaskov
    Division of Cell and Molecular Biology, Toronto General Research Institute, University Health Network, 200 Elizabeth Street, MBRC 4R402 Toronto, Ontario, Canada M5G 2C4
    Endocrinology 147:3398-407. 2006
    ..The results suggest that activation of the UPR may significantly contribute to palmitate- but not oleate-induced pancreatic beta-cell death...
  21. ncbi Free fatty acids and cytokines induce pancreatic beta-cell apoptosis by different mechanisms: role of nuclear factor-kappaB and endoplasmic reticulum stress
    Ilham Kharroubi
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Route de Lennik, 808 CP 618, B 1070 Brussels, Belgium
    Endocrinology 145:5087-96. 2004
    ..Our results argue against a unifying hypothesis for the mechanisms of beta-cell death in T1DM and T2DM...
  22. ncbi beta-Cell death during progression to diabetes
    D Mathis
    Section on Immunology and Immunogenetics, Joslin Diabetes Centre, One Joslin Place, Boston, Massachusetts 02215, USA
    Nature 414:792-8. 2001
    ..beta-Cell apoptosis may also be involved in the occasional evolution of type 2 into type 1 diabetes...
  23. doi Voltage-gated ion channels in human pancreatic beta-cells: electrophysiological characterization and role in insulin secretion
    Matthias Braun
    Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK
    Diabetes 57:1618-28. 2008
    ..To characterize the voltage-gated ion channels in human beta-cells from nondiabetic donors and their role in glucose-stimulated insulin release...
  24. ncbi Diabetes mellitus and exocrine pancreatic dysfunction in perk-/- mice reveals a role for translational control in secretory cell survival
    H P Harding
    Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 10016, New York, NY, USA
    Mol Cell 7:1153-63. 2001
    ..These findings suggest a special role for translational control in protecting secretory cells from ER stress...
  25. ncbi Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets
    N Lumelsky
    Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4092, USA
    Science 292:1389-94. 2001
    ..In pancreas, insulin is produced and secreted by specialized structures, islets of Langerhans. Diabetes, which affects 16 million people in the United States, results from abnormal function of ..
  26. ncbi Type 2 diabetes-a matter of beta-cell life and death?
    Christopher J Rhodes
    Pacific Northwest Research Institute, 720 Broadway, Seattle, WA 98122, USA
    Science 307:380-4. 2005
    ..Thus, the IRS-2 pathway appears to be a crucial participant in the tenuous balance between effective pancreatic beta-cell mass and insulin resistance...
  27. ncbi Expression of chemokines, CXC chemokine ligand 10 (CXCL10) and CXCR3 in the inflamed islets of patients with recent-onset autoimmune type 1 diabetes
    Sae Uno
    Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2 2 B5 Yamadaoka, Suita, Japan
    Endocr J 57:991-6. 2010
    ..The interaction of CXCL10 and CXCR3 would contribute to the selective destruction of beta cells in the development of type 1 diabetes...
  28. ncbi Minireview: Secondary beta-cell failure in type 2 diabetes--a convergence of glucotoxicity and lipotoxicity
    Vincent Poitout
    Pacific Northwest Research Institute, Seattle, Washington 98122, USA
    Endocrinology 143:339-42. 2002
    ..We propose that chronic hyperglycemia, independent of hyperlipidemia, is toxic for beta-cell function, whereas chronic hyperlipidemia is deleterious only in the context of concomitant hyperglycemia...
  29. ncbi Lipid membranes modulate the structure of islet amyloid polypeptide
    Sajith A Jayasinghe
    Department of Biochemistry and Molecular Biology, Zilkha Neurogenetic Institute, University of Southern California, 1501 San Pablo Street, Los Angeles, California 90033, USA
    Biochemistry 44:12113-9. 2005
    ..The potential roles of IAPP-membrane interaction and the novel membrane-bound alpha-helical conformation in IAPP aggregation are discussed...
  30. ncbi The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes
    S E Kahn
    Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle, Washington, USA
    Diabetologia 46:3-19. 2003
    ....
  31. doi Microscopic anatomy of the human islet of Langerhans
    Peter In't Veld
    Department of Pathology, Vrije Universiteit Brussel, B 1090 Brussels, Belgium
    Adv Exp Med Biol 654:1-19. 2010
    Human islets of Langerhans are complex micro-organs responsible for maintaining glucose homeostasis...
  32. ncbi A choice of death--the signal-transduction of immune-mediated beta-cell apoptosis
    D L Eizirik
    Gene Expression Unit, Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, Belgium
    Diabetologia 44:2115-33. 2001
    ..A detailed characterization of these "gene modules", and of the signalling pathways and transcription factors regulating them could allow us to understand the ultimate mechanisms leading to beta-cell apoptosis...
  33. ncbi Assessment of human pancreatic islet architecture and composition by laser scanning confocal microscopy
    Marcela Brissova
    Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism, 715 PRB, Vanderbilt University, Nashville, TN 37232, USA
    J Histochem Cytochem 53:1087-97. 2005
    ..The results indicate that human islets not only are quite heterogeneous in terms of cell composition but also have a substantially different architecture from widely studied murine islets...
  34. ncbi The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients
    P Marchetti
    Department of Endocrinology and Metabolism, Metabolic Unit, Ospedale Cisanello, University of Pisa, Via Paradisa 2, 56100, Pisa, Italy
    Diabetologia 50:2486-94. 2007
    ..Since ER stress has been associated with beta cell dysfunction, we studied several features of beta cell ER in human type 2 diabetes...
  35. 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...
  36. ncbi Induction of pancreatic differentiation by signals from blood vessels
    E Lammert
    Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA
    Science 294:564-7. 2001
    ..These results indicate that vessels not only provide metabolic sustenance, but also provide inductive signals for organ development...
  37. pmc Insulin promoter DNA methylation correlates negatively with insulin gene expression and positively with HbA(1c) levels in human pancreatic islets
    B T Yang
    Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, University Hospital Malmoe, 205 02 Malmoe, Sweden
    Diabetologia 54:360-7. 2011
    ..Here, we examined DNA methylation of the insulin gene promoter in pancreatic islets from patients with type 2 diabetes and non-diabetic human donors and related it to insulin expression, HbA(1c) levels, BMI and age...
  38. pmc Pancreatic islet autoantibodies as predictors of type 1 diabetes in the Diabetes Prevention Trial-Type 1
    Tihamer Orban
    Joslin Diabetes Center, Boston, Massachusetts, USA
    Diabetes Care 32:2269-74. 2009
    ..Thus, we studied the extent to which specific autoantibodies are predictive of type 1 diabetes...
  39. ncbi Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets: evidence that beta-cell death is caspase mediated, partially dependent on ceramide pathway, and Bcl-2 regulated
    Roberto Lupi
    Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy
    Diabetes 51:1437-42. 2002
    ..The cytostatic action is likely to be due to the FFA-induced reduction of intraislet glucose metabolism, and the proapoptotic effects are mostly caspase mediated, partially dependent on ceramide pathway, and possibly Bcl-2 regulated...
  40. ncbi Oxidative stress, ER stress, and the JNK pathway in type 2 diabetes
    Hideaki Kaneto
    Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2 2 Yamadaoka, Suita, Osaka, 565 0871, Japan
    J Mol Med (Berl) 83:429-39. 2005
    ..Thus, the JNK pathway plays a central role in pathogenesis of type 2 diabetes and may be a potential target for diabetes therapy...
  41. pmc Dendritic cell-expanded, islet-specific CD4+ CD25+ CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice
    Kristin V Tarbell
    Laboratory of Cellular Physiology and Immunology and Christopher H Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021, USA
    J Exp Med 204:191-201. 2007
    ..Therefore, inoculation of DC-expanded, antigen-specific suppressor T cells has considerable efficacy in ameliorating ongoing diabetes in NOD mice...
  42. ncbi Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors
    Guoqiang Gu
    Department of Molecular and Cellular Biology, and Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA
    Development 129:2447-57. 2002
    ..5 (E9.5-E11.5). These findings suggest that lineages for exocrine, endocrine islet and duct progenitors are committed at mid-gestation...
  43. pmc Carbonic anhydrase II-positive pancreatic cells are progenitors for both endocrine and exocrine pancreas after birth
    Akari Inada
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 105:19915-9. 2008
    ..This identification of a differentiated pancreatic cell type as an in vivo progenitor of all differentiated pancreatic cell types has implications for a potential expandable source for new islets for replenishment therapy for diabetes...
  44. ncbi Mitochondrial dysfunction and type 2 diabetes
    Bradford B Lowell
    Department of Medicine, Beth Israel Deaconess Medical Center, 99 Brookline Avenue, Harvard Medical School, Boston, MA 02215, USA
    Science 307:384-7. 2005
    ..Emerging evidence supports the potentially unifying hypothesis that both of these prominent features of type 2 diabetes are caused by mitochondrial dysfunction...
  45. pmc The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells
    Patrick Collombat
    Department of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg, D 37077 Gottingen, Germany
    Cell 138:449-62. 2009
    ....
  46. ncbi Transgenic expression of antioxidant protein thioredoxin in pancreatic beta cells prevents progression of type 2 diabetes mellitus
    Mayu Yamamoto
    Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, Osaka, Japan
    Antioxid Redox Signal 10:43-9. 2008
    ....
  47. ncbi Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates
    Bernhard J Hering
    Diabetes Institute for Immunology and Transplantation, Department of Surgery, University of Minnesota, 424 Harvard Street SE, Minneapolis, Minnesota 55455, USA
    Nat Med 12:301-3. 2006
    ....
  48. ncbi A pancreatic islet-specific microRNA regulates insulin secretion
    Matthew N Poy
    Laboratory of Metabolic Diseases and Laboratory of RNA Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 432:226-30. 2004
    ..Thus, miR-375 is a regulator of insulin secretion and may thereby constitute a novel pharmacological target for the treatment of diabetes...
  49. pmc Induction of human beta-cell proliferation and engraftment using a single G1/S regulatory molecule, cdk6
    Nathalie M Fiaschi-Taesch
    Division of Endocrinology, The University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Diabetes 59:1926-36. 2010
    ..We explored the presence, subcellular localization, and function of five early G1/S phase molecules-cyclins D1-3 and cdk 4 and 6-in the adult human beta-cell...
  50. doi Unraveling the role of the ghrelin gene peptides in the endocrine pancreas
    Riccarda Granata
    Laboratory of Molecular, Cellular Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Corso Dogliotti 14, 10126 Turin, Italy
    J Mol Endocrinol 45:107-18. 2010
    ..The present review summarizes the newest findings on AG, UAG, and Ob expression in pancreatic islets and the role of these peptides on beta-cell development, survival, and function...
  51. ncbi Glucose-stimulated signaling pathways in biphasic insulin secretion
    Susanne G Straub
    Cornell University, Ithaca, New York, USA
    Diabetes Metab Res Rev 18:451-63. 2002
    ..Agonists that can change the rate-limiting steps for both phases of insulin release include those like glucagon-like peptide 1 (GLP-1) that raise cyclic AMP levels and those like acetylcholine that act via DAG...
  52. ncbi Response of human islets to isolation stress and the effect of antioxidant treatment
    Rita Bottino
    Department of Pediatrics, University of Pittsburgh, School of Medicine, Pennsylvania, USA
    Diabetes 53:2559-68. 2004
    The process of human islet isolation triggers a cascade of stressful events in the islets of Langerhans involving activation of apoptosis and necrosis and the production of proinflammatory molecules that negatively influence islet yield ..
  53. pmc Tissue-specific alternative splicing of TCF7L2
    Ludmila Prokunina-Olsson
    Genome Technology Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA
    Hum Mol Genet 18:3795-804. 2009
    ..Alternative splicing of TCF7L2 in pancreatic islets warrants future studies. GenBank Accession Numbers: FJ010164-FJ010174...
  54. pmc Glucose- and hormone-induced cAMP oscillations in α- and β-cells within intact pancreatic islets
    Geng Tian
    Department of Medical Cell Biology, Biomedical Centre, Uppsala University, Uppsala, Sweden
    Diabetes 60:1535-43. 2011
    cAMP is a critical messenger for insulin and glucagon secretion from pancreatic β- and α-cells, respectively. Dispersed β-cells show cAMP oscillations, but the signaling kinetics in cells within intact islets of Langerhans is unknown.
  55. doi Expression of islet-specific microRNAs during human pancreatic development
    Mugdha V Joglekar
    Stem Cells and Diabetes Section, Lab 12, National Center for Cell Science, Ganeshkhind Road, Pune, MH 411007, India
    Gene Expr Patterns 9:109-13. 2009
    ..Our data demonstrate that miRNAs that are known to be regulated during Zebrafish pancreatic development may play similar role in human pancreatic islet development...
  56. ncbi Adaptation of islets of Langerhans to pregnancy: beta-cell growth, enhanced insulin secretion and the role of lactogenic hormones
    R L Sorenson
    Department of Cell Biology and Neuroanatomy, University of Minnesota Medical School, Minneapolis 55455, USA
    Horm Metab Res 29:301-7. 1997
    ..A model for how lactogens up-regulate islets during pregnancy is proposed...
  57. ncbi Impaired insulin secretion and beta-cell loss in tissue-specific knockout mice with mitochondrial diabetes
    J P Silva
    Department of Molecular Medicine, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden
    Nat Genet 26:336-40. 2000
    ..This animal model reproduces the beta-cell pathology of human mitochondrial diabetes and provides genetic evidence for a critical role of the respiratory chain in insulin secretion...
  58. pmc Glucose suppression of glucagon secretion: metabolic and calcium responses from alpha-cells in intact mouse pancreatic islets
    Sylvain J Le Marchand
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 285:14389-98. 2010
    ..Taken together, the data suggest that suppression occurs downstream from alpha-cell calcium signaling, presumably at the level of vesicle trafficking or exocytotic machinery...
  59. ncbi Functional and molecular defects of pancreatic islets in human type 2 diabetes
    Silvia Del Guerra
    Department of Endocrinology and Metabolism, Metabolic Unit, Ospedale Cisanello, Via Paradisa 2, 56124 Pisa, Italy
    Diabetes 54:727-35. 2005
    ..In this regard, it is suggested that reducing islet cell oxidative stress is a potential target of human type 2 diabetes therapy...
  60. ncbi Triggering and amplifying pathways of regulation of insulin secretion by glucose
    J C Henquin
    Unité d Endocrinologie et Métabolisme, University of Louvain Faculty of Medicine, Brussels, Belgium
    Diabetes 49:1751-60. 2000
    ..Besides the available drugs that act on K(ATP) channels and increase the triggering signal, novel drugs that correct a deficient amplifying pathway would be useful to restore adequate insulin secretion in type 2 diabetic patients...
  61. ncbi Structural and functional abnormalities in the islets isolated from type 2 diabetic subjects
    Shaoping Deng
    Department of Surgery, Harrison Department of Surgical Research, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Diabetes 53:624-32. 2004
    ..These results provide direct evidence for abnormalities in the islets of type 2 diabetic patients that may contribute to the pathogenesis of the disease...
  62. ncbi Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9-deficient mice
    K A Harrison
    Laboratory of Immunoregulation National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Genet 23:71-5. 1999
    ..During mouse development, the dorsal and ventral pancreatic buds and mature beta-cells in the islets of Langerhans express Hlxb9...
  63. ncbi GLP-1 inhibits and adrenaline stimulates glucagon release by differential modulation of N- and L-type Ca2+ channel-dependent exocytosis
    Yang Z De Marinis
    Lund University Diabetes Centre, Department of Clinical Sciences, Clinical Research Centre, Lund University, SE20502 Malmö, Sweden
    Cell Metab 11:543-53. 2010
    ..Adrenaline stimulates L-type Ca(2+) channel-dependent exocytosis by activation of the low-affinity cAMP sensor Epac2 via a large increase in [cAMP](i)...
  64. 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...
  65. ncbi Mesenchymal stem cell and islet co-transplantation promotes graft revascularization and function
    Taihei Ito
    Southern California Islet Cell Resources Center, Department of Diabetes, Endocrinology, and Metabolism, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA
    Transplantation 89:1438-45. 2010
    ..Bone marrow-derived mesenchymal stem cells (MSCs) are known to produce vascular endothelial growth factor. We hypothesize that co-transplantation of MSCs and islets promotes revascularization and improves islet graft function...
  66. pmc Analysis of islet inflammation in human type 1 diabetes
    A Willcox
    Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Tamar Science Park, Plymouth, UK
    Clin Exp Immunol 155:173-81. 2009
    ..Natural killer cells and forkhead box protein P3(+) T cells do not appear to be required for beta cell death...
  67. ncbi Type 2 diabetes: principles of pathogenesis and therapy
    Michael Stumvoll
    Third Medical Department, University of Leipzig, Leipzig, Germany
    Lancet 365:1333-46. 2005
    ..Management includes not only diet and exercise, but also combinations of anti-hyperglycaemic drug treatment with lipid-lowering, antihypertensive, and anti platelet therapy...
  68. ncbi Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation
    Yuval Dor
    Department of Molecular and Cellular Biology and Howard Hughes Medical Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
    Nature 429:41-6. 2004
    ..These results suggest that terminally differentiated beta-cells retain a significant proliferative capacity in vivo and cast doubt on the idea that adult stem cells have a significant role in beta-cell replenishment...
  69. pmc Impaired insulin secretion and glucose tolerance in beta cell-selective Ca(v)1.2 Ca2+ channel null mice
    Verena Schulla
    Institut fur Pharmakologie und Toxikologie, TU Munchen, Biedersteiner Strasse 29, D 80802 München, Germany
    EMBO J 22:3844-54. 2003
    ..2 channel. Thus, the conduit of Ca(2+) entry determines the ability of the cation to elicit secretion...
  70. ncbi Glucagon-like peptide-1 promotes islet cell growth and inhibits apoptosis in Zucker diabetic rats
    Loredana Farilla
    Cedars Sinai Medical Center, Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Los Angeles, California 90048, USA
    Endocrinology 143:4397-408. 2002
    ..Our findings provide evidence that the beneficial effects of GLP-1 in Zucker diabetic rats is mediated by an increase in islet cell proliferation and a decrease of cellular apoptosis...
  71. ncbi Malonyl-CoA signaling, lipid partitioning, and glucolipotoxicity: role in beta-cell adaptation and failure in the etiology of diabetes
    Marc Prentki
    Molecular Nutrition Unit, Department of Nutrition, University of Montreal, the Centre de Recherche du CHUM, Montreal, Quebec, Canada
    Diabetes 51:S405-13. 2002
    ....
  72. ncbi Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese Type II diabetic patients
    H Sakuraba
    Department of Pathology, Hirosaki University School of Medicine, 5 Zaifu cho, Hirosaki, 036 8562 Japan
    Diabetologia 45:85-96. 2002
    ..We examined the pancreatic islet lesions in Japanese patients with Type II diabetes mellitus to determine if the damage was related to oxidative stress...
  73. pmc Islet amyloid in type 2 diabetes, and the toxic oligomer hypothesis
    Leena Haataja
    Larry Hillblom Islet Research Center, UCLA David Geffen School of Medicine, 900 Weyburn Place A, Los Angeles, California 90024 2852, USA
    Endocr Rev 29:303-16. 2008
    ....
  74. ncbi Different effects of FK506, rapamycin, and mycophenolate mofetil on glucose-stimulated insulin release and apoptosis in human islets
    James D Johnson
    Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada
    Cell Transplant 18:833-45. 2009
    ..Together, our results demonstrate that immunosuppressants impair human beta-cell function and survival, and that these defects can be circumvented to a certain extent with exenatide treatment...
  75. ncbi Gastrin stimulates beta-cell neogenesis and increases islet mass from transdifferentiated but not from normal exocrine pancreas tissue
    Ilse Rooman
    Cell Differentiation Group, Diabetes Research Center, Free University of Brussels VUB, Brussels, Belgium
    Diabetes 51:686-90. 2002
    ..In conclusion, we demonstrate that administration of gastrin stimulates beta-cell neogenesis and expansion of the beta-cell mass from transdifferentiated exocrine pancreas...
  76. ncbi Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and beta-cell dysfunction
    G Boden
    Division of Endocrinology Diabetes Metabolism and the General Clinical Research Center, Temple University Hospital, Philadelphia PA 19140, USA
    Eur J Clin Invest 32:14-23. 2002
    ....
  77. ncbi The role for endoplasmic reticulum stress in diabetes mellitus
    Decio L Eizirik
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Route de Lennik, 808 CP 618, 1070 Brussels, Belgium
    Endocr Rev 29:42-61. 2008
    ..A better understanding of the pathways regulating ER stress in beta-cells may be instrumental for the design of novel therapies to prevent beta-cell loss in diabetes...
  78. pmc Sustained Neurog3 expression in hormone-expressing islet cells is required for endocrine maturation and function
    Sui Wang
    Program in Developmental Biology and Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Proc Natl Acad Sci U S A 106:9715-20. 2009
    ..These findings demonstrate that Neurog3 is required not only for initiating endocrine cell differentiation, but also for promoting islet cell maturation and maintaining islet function...
  79. ncbi Endoplasmic reticulum stress and the development of diabetes: a review
    Heather P Harding
    Skirball Institute, New York University School of Medicine, New York, New York 10016, USA
    Diabetes 51:S455-61. 2002
    ..We will review this and other rare forms of clinical and experimental diabetes and consider the role of ER stress in the development of more common forms of the disease...
  80. ncbi Palmitate induces a pro-inflammatory response in human pancreatic islets that mimics CCL2 expression by beta cells in type 2 diabetes
    M Igoillo-Esteve
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, CP 618, Route de Lennik 808, 1070, Brussels, Belgium
    Diabetologia 53:1395-405. 2010
    ..One of the proposed mechanisms of beta cell failure is local inflammation, but the presence of pancreatic islet inflammation in type 2 diabetes and the mechanisms involved remain under debate...
  81. ncbi Mitochondrial reactive oxygen species reduce insulin secretion by pancreatic beta-cells
    Koji Sakai
    Department of Metabolic Medicine, Kumamoto University School of Medicine, 1 1 1 Honjo, Japan
    Biochem Biophys Res Commun 300:216-22. 2003
    ..We propose that mitochondrial overwork is a potential mechanism causing impaired first-phase of GIIS in the early stages of diabetes mellitus...
  82. ncbi Monounsaturated fatty acids prevent the deleterious effects of palmitate and high glucose on human pancreatic beta-cell turnover and function
    Kathrin Maedler
    Division of Endocrinology and Diabetes, Department of Medicine, University Hospital, CH 8091 Zurich, Switzerland
    Diabetes 52:726-33. 2003
    ..The deleterious effect of palmitic acid is mediated via formation of ceramide and activation of the apoptotic mitochondrial pathway, whereas Bcl-2 may contribute to the protective effect of monounsaturated fatty acids...
  83. ncbi Islet endothelial cells and pancreatic beta-cell proliferation: studies in vitro and during pregnancy in adult rats
    Magnus Johansson
    Department of Medical Cell Biology, Biomedical Center, Uppsala, Sweden
    Endocrinology 147:2315-24. 2006
    ..e. coinciding with the peak of beta-cell proliferation. In summary, our results suggest the existence of an endothelial-endocrine axis within adult pancreatic islets, which is of importance for adult beta-cell proliferation...
  84. pmc PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistance
    Rohit N Kulkarni
    Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Clin Invest 114:828-36. 2004
    ..This study shows that, in postdevelopmental states of beta cell growth, PDX-1 is a critical regulator of beta cell replication and is required for the compensatory response to insulin resistance...
  85. doi Unique splicing pattern of the TCF7L2 gene in human pancreatic islets
    P Osmark
    Department of Clinical Sciences, CRC Malmö University Hospital, Lund University, Malmo, Sweden
    Diabetologia 52:850-4. 2009
    ..Here, the detailed TCF7L2 splicing pattern in five human tissues is described and dependence on risk genotype explored...
  86. ncbi Beta-cell adaptation and decompensation during the progression of diabetes
    G C Weir
    Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Diabetes 50:S154-9. 2001
    ..Arguments are developed that the beta-cell changes found in diabetes are better correlated with increased glucose levels than with non-esterified fatty acid levels, thus supporting the importance of glucose toxicity...
  87. ncbi High glucose causes apoptosis in cultured human pancreatic islets of Langerhans: a potential role for regulation of specific Bcl family genes toward an apoptotic cell death program
    M Federici
    Laboratory of Molecular Medicine, Department of Internal Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
    Diabetes 50:1290-301. 2001
    ..These data suggest that in human islets, high glucose may modulate the balance of proapoptotic and antiapoptotic Bcl proteins toward apoptosis, thus favoring beta-cell death...
  88. ncbi Functional and morphological alterations of mitochondria in pancreatic beta cells from type 2 diabetic patients
    M Anello
    Internal Medicine, Department of Internal and Specialistic Medicine, University of Catania, Ospedale Cannizzaro, Catania, Italy
    Diabetologia 48:282-9. 2005
    ....
  89. doi A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets
    Jalal Taneera
    Lund University Diabetes Center, Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital Malmö, Lund University, Malmo 20502, Sweden
    Cell Metab 16:122-34. 2012
    ..The data present a global map of genes associated with islet dysfunction and demonstrate the value of systems genetics for the identification of genes potentially involved in T2D...
  90. 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...
  91. ncbi Glucagon-like peptide 1 induces pancreatic beta-cell proliferation via transactivation of the epidermal growth factor receptor
    Jean Buteau
    Molecular Nutrition Unit, Departments of Nutrition and Biochemistry, University of Montreal, the Centre de Recherche du CHUM and Institut du Cancer, Montreal, Quebec, Canada
    Diabetes 52:124-32. 2003
    ....
  92. pmc Islet formation during the neonatal development in mice
    Kevin Miller
    Department of Medicine, The University of Chicago, Chicago, IL, USA
    PLoS ONE 4:e7739. 2009
    ..Mathematical modeling of the fission process in the neonatal islet formation is also presented...
  93. pmc Unique arrangement of alpha- and beta-cells in human islets of Langerhans
    Domenico Bosco
    Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and University of Geneva, Geneva, Switzerland
    Diabetes 59:1202-10. 2010
    ..However, a clear description of human islet architecture has not yet been reported. The aim of this work was to describe our observations on the arrangement of human islet cells...
  94. ncbi Persistent improvement of type 2 diabetes in the Goto-Kakizaki rat model by expansion of the beta-cell mass during the prediabetic period with glucagon-like peptide-1 or exendin-4
    Cécile Tourrel
    LPPN, CNRS UMR 7059, Universite Paris 7, Paris, France
    Diabetes 51:1443-52. 2002
    ..Under these conditions, GLP-1 represents a unique tool because of its beta-cell replenishing effect in spontaneously diabetic rodents. It may prove to be an invaluable agent for the prevention of human type 2 diabetes...
  95. ncbi Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1
    Jun Nakae
    Naomi Berrie Diabetes Center, Berrie Research Pavilion, 1150 St Nicholas Avenue, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    Nat Genet 32:245-53. 2002
    ..This has been corrected in the full-text online version of the article. The name will appear correctly in the print version...
  96. pmc MafA is a key regulator of glucose-stimulated insulin secretion
    Chuan Zhang
    Institute of Basic Medical Sciences and Laboratory Animal Resource Center, University of Tsukuba, 1 1 1 Tennodai, Tsukuba 305 8575, Japan
    Mol Cell Biol 25:4969-76. 2005
    ..Further analysis revealed that insulin 1, insulin 2, Pdx1, Beta2, and Glut-2 transcripts are diminished in MafA-deficient mice. These results show that MafA is a key regulator of glucose-stimulated insulin secretion in vivo...
  97. ncbi Temporal control of neurogenin3 activity in pancreas progenitors reveals competence windows for the generation of different endocrine cell types
    Kerstin A Johansson
    Swiss Institute for Experimental Cancer Research, 155 ch des Boveresses, 1066 Epalinges, Switzerland
    Dev Cell 12:457-65. 2007
    ..We further show that the progenitors acquire competence to generate late-born cells in a mechanism that is intrinsic to the epithelium...
  98. ncbi Mechanism of insulin gene regulation by the pancreatic transcription factor Pdx-1: application of pre-mRNA analysis and chromatin immunoprecipitation to assess formation of functional transcriptional complexes
    Tessy Iype
    Department of Internal Medicine and the Diabetes Center, University of Virginia, Charlottesville, Virginia 22908, USA
    J Biol Chem 280:16798-807. 2005
    ..This complex leads to enhancement of elongation by the basal transcriptional machinery...
  99. ncbi Major histocompatibility complex class I molecules are required for the development of insulitis in non-obese diabetic mice
    J Katz
    Laboratoire de Genetique Moleculaire des Eucaryotes du CNRS, Strasbourg, France
    Eur J Immunol 23:3358-60. 1993
    An early step in the development of autoimmune diabetes is lymphocyte infiltration into the islets of Langerhans of the pancreas, or insulitis...
  100. pmc Responses against islet antigens in NOD mice are prevented by tolerance to proinsulin but not IGRP
    Balasubramanian Krishnamurthy
    St Vincent s Institute, Fitzroy, Victoria, Australia
    J Clin Invest 116:3258-65. 2006
    ..Our results suggest that pathogenic proinsulin-specific immunity in NOD mice subsequently spreads to other antigens such as IGRP...
  101. pmc Involvement of Per-Arnt-Sim Kinase and extracellular-regulated kinases-1/2 in palmitate inhibition of insulin gene expression in pancreatic beta-cells
    Ghislaine Fontes
    Montreal Diabetes Research Center, CRCHUM, University of Montreal, Quebec, Canada
    Diabetes 58:2048-58. 2009
    ..This study aimed to ascertain the role of extracellular-regulated kinases (ERKs)1/2, protein kinase B (PKB), and Per-Arnt-Sim kinase (PASK) in palmitate inhibition of insulin gene expression in pancreatic beta-cells...

Research Grants83

  1. Gene-engineered dendritic cell therapy for diabetics
    Massimo Trucco; Fiscal Year: 2006
    ..disease whose etiopathogenesis lies in the selective destruction of the insulin-producing beta cells of the islets of Langerhans in the pancreas...
  2. Beta Cell Adaptation to Stress in Baboon Pancreas After Partial Pancreatectomy
    Franco Folli; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): Deposition of islet amyloid pancreatic polypeptide (IAPP) in the islets of Langerhans is the characteristic feature of human type 2 diabetic pancreas but represents the final stage of a process ..
  3. IMMUNOCHEMICAL MODULATION OF METABOLIC HOMEOSTASIS
    Vernon Grund; Fiscal Year: 1991
    ..metabolic homeostasis through specific histamine receptor interactions on adipocytes, hepatocytes, and islets of Langerhans. The project will focus on mechanisms by which histamine, through interaction with specific membrane ..
  4. New Solutions Islet Recovery Preservation of Pancreas
    Michael Taylor; Fiscal Year: 2006
    unreadable] DESCRIPTION (provided by applicant): Transplantation of islets of Langerhans for the clinical treatment of Type I diabetes has had a resurgence of interest due to results obtained using the "Edmonton protocol"...
  5. New Solutions to Improve Islet Recovery after Machine Preservation of Pancreas
    Michael Taylor; Fiscal Year: 2009
    Transplantation of islets of Langerhans for the clinical treatment of Type I diabetes has had a resurgence of interest due to results obtained using the "Edmonton protocol"...
  6. New Solutions to Improve Islet Recovery after Machine Preservation of Pancreas
    Michael Taylor; Fiscal Year: 2007
    unreadable] DESCRIPTION (provided by applicant): Transplantation of islets of Langerhans for the clinical treatment of Type I diabetes has had a resurgence of interest due to results obtained using the "Edmonton protocol"...
  7. Nkx2.2 in Pancreatic Development: The Role of the NK2-SD Domain
    JOSHUA ADAM LEVINE; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): The endocrine pancreas, composed of the islets of Langerhans, is responsible for the maintenance of blood glucose homeostasis. Several cell types comprise the islets and include glucagon-producing ...
  8. Beta Cell Adaptation to Stress in Baboon Pancreas After Partial Pancreatectomy
    FRANCO BATTISTA FOLLI; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Deposition of islet amyloid pancreatic polypeptide (IAPP) in the islets of Langerhans is the characteristic feature of human type 2 diabetic pancreas but represents the final stage of a process ..
  9. Prevention of Type I Diabetes Mellitus using a Cell Vac*
    Nick Giannoukakis; Fiscal Year: 2002
    ..disease whose etiopathogenesis lies in the selective destruction of the insulin-producing beta cells of the islets of Langerhans in the pancreas...
  10. Type I Diabetes Mellitus Prevention using Cell Vaccine
    Nick Giannoukakis; Fiscal Year: 2001
    ..disease whose etiopathogenesis lies in the selective destruction of the insulin-producing beta cells of the islets of Langerhans in the pancreas...
  11. Prevention of Type 1 Diabetes with MMP Inhibitors
    David Bleich; Fiscal Year: 2003
    Lymphocyte infiltrates in the islets of Langerhans, "insulitis", is a characteristic hallmark of immune-mediated diabetes in rodent models and human beings...
  12. Anti-apoptotic gene therapy: Islet allotransplantation
    Nick Giannoukakis; Fiscal Year: 2001
    ..mellitus (IDDM) is an autoimmune disease that specifically targets the pancreatic beta cells of the islets of Langerhans in a T-lymphocyte-mediated destruction...
  13. Anti-apoptotic gene therapy: Islet allotransplantation
    Nick Giannoukakis; Fiscal Year: 2002
    ..mellitus (IDDM) is an autoimmune disease that specifically targets the pancreatic beta cells of the islets of Langerhans in a T-lymphocyte-mediated destruction...
  14. Immune Tolerance Against Type I Diabetes in Mice
    Habib Zaghouani; Fiscal Year: 2006
    Type I diabetes (T1D) is a spontaneous autoimmune disease in which the insulin-producing beta cells of the islets of langerhans are destroyed as a consequence of inflammatory reactions triggered by genetic and environmental factors...
  15. Immune Tolerance Against Type I Diabetes in Mice
    Habib Zaghouani; Fiscal Year: 2007
    Type I diabetes (T1D) is a spontaneous autoimmune disease in which the insulin-producing beta cells of the islets of langerhans are destroyed as a consequence of inflammatory reactions triggered by genetic and environmental factors...
  16. Immune Tolerance Against Type I Diabetes in Mice
    Habib Zaghouani; Fiscal Year: 2005
    Type I diabetes (T1D) is a spontaneous autoimmune disease in which the insulin-producing beta cells of the islets of langerhans are destroyed as a consequence of inflammatory reactions triggered by genetic and environmental factors...
  17. ENGINEERED GLUCOSE METABOLISM IN INSULIN-SECRETING CELLS
    Christopher Newgard; Fiscal Year: 1993
    ..secretion occurs as a result of, and in proportion to, the rate of glucose metabolism in beta-cells of the islets of Langerhans. This proposal seeks to utilize techniques of molecular biology to alter the rate and regulation of glucose ..
  18. REGULATORY T AND B CELL CIRCUITS IN TRANSPLANTATION
    Joshua Miller; Fiscal Year: 1992
    ..vitro T cell lymphoproliferative reactions to purified suspensions of kidney tubular cells and cells from Islets of Langerhans, the latter complementing our clinical trial recently reinstituted of islet transplantation in type I ..
  19. REGULATORY T AND B CELL CIRCUITS IN TRANSPLANTATION
    Joshua Miller; Fiscal Year: 1991
    ..vitro T cell lymphoproliferative reactions to purified suspensions of kidney tubular cells and cells from Islets of Langerhans, the latter complementing our clinical trial recently reinstituted of islet transplantation in type I ..
  20. REGULATORY T AND B CELL CIRCUITS IN TRANSPLANTATION
    Joshua Miller; Fiscal Year: 1993
    ..vitro T cell lymphoproliferative reactions to purified suspensions of kidney tubular cells and cells from Islets of Langerhans, the latter complementing our clinical trial recently reinstituted of islet transplantation in type I ..
  21. Myt1 Function for Endocrine Islet Development & Fuction
    Guoqiang Gu; Fiscal Year: 2007
    ..digestive enzymes to the duodenum; four types of endocrine cells ( 13,5, and PP cells) form endocrine islets of Langerhans, which secrete endocrine hormones to regulate a variety of physiological processes...
  22. Myt1 Function for Endocrine Islet Development & Fuction
    Guoqiang Gu; Fiscal Year: 2006
    ..digestive enzymes to the duodenum; four types of endocrine cells ( 13,5, and PP cells) form endocrine islets of Langerhans, which secrete endocrine hormones to regulate a variety of physiological processes...
  23. Myt1 Function for Endocrine Islet Development & Fuction
    Guoqiang Gu; Fiscal Year: 2005
    ..digestive enzymes to the duodenum; four types of endocrine cells ( 13,5, and PP cells) form endocrine islets of Langerhans, which secrete endocrine hormones to regulate a variety of physiological processes...
  24. Myt1 Function for Endocrine Islet Development & Fuction
    Guoqiang Gu; Fiscal Year: 2004
    ..digestive enzymes to the duodenum; four types of endocrine cells ( 13,5, and PP cells) form endocrine islets of Langerhans, which secrete endocrine hormones to regulate a variety of physiological processes...
  25. Prevention of Type 1 Diabetes with MMP Inhibitors
    David Bleich; Fiscal Year: 2002
    Lymphocyte infiltrates in the islets of Langerhans, "insulitis", is a characteristic hallmark of immune-mediated diabetes in rodent models and human beings...
  26. Prevention of Type 1 Diabetes with MMP Inhibitors
    David Bleich; Fiscal Year: 2003
    Lymphocyte infiltrates in the islets of Langerhans, "insulitis", is a characteristic hallmark of immune-mediated diabetes in rodent models and human beings...
  27. PHOSPHOLIPASES AND INSULIN SECRETION
    Bryan Wolf; Fiscal Year: 1999
    ..role of phospholipases and heterotrimeric GTP-binding proteins in insulin secretion by the beta-cells of islets of Langerhans. The metabolism of glucose is sufficient for insulin secretion by islets of Langerhans...
  28. Gene-engineered dendritic cell therapy for diabetics
    Massimo Trucco; Fiscal Year: 2005
    ..disease whose etiopathogenesis lies in the selective destruction of the insulin-producing beta cells of the islets of Langerhans in the pancreas...
  29. Gene-engineered dendritic cell therapy for diabetics
    Massimo Trucco; Fiscal Year: 2003
    ..disease whose etiopathogenesis lies in the selective destruction of the insulin-producing beta cells of the islets of Langerhans in the pancreas...
  30. Gene-engineered dendritic cell therapy for diabetics
    Massimo Trucco; Fiscal Year: 2002
    ..disease whose etiopathogenesis lies in the selective destruction of the insulin-producing beta cells of the islets of Langerhans in the pancreas...
  31. STUDIES OF PANCREAS TRANSPLANTATION IN DIABETES
    MARSHALL ORLOFF; Fiscal Year: 1980
    ..to be learned about the etiology and pathogenesis of diabetes, transplantation of the whole pancreas or islets of Langerhans represents potential means of curing the conditions that are worthy of serious investigation...
  32. Pre-Conditioning Pancreatic Islets for Transplantation
    Ginny Bumgardner; Fiscal Year: 2005
    ..children and young adults which results from thedestruction of insulin-producing beta (beta) cells of the islets of Langerhans in the pancreas...
  33. Pre-Conditioning Pancreatic Islets for Transplantation
    Ginny Bumgardner; Fiscal Year: 2006
    ..children and young adults which results from thedestruction of insulin-producing beta (beta) cells of the islets of Langerhans in the pancreas...
  34. PUTATIVE MEDIATORS OF INSULIN SECRETION
    SUZANNE LAYCHOCK; Fiscal Year: 1993
    Insulin secretion from beta cells of islets of Langerhans is mediated by second messengers such as cyclic AMP, cyclic CMP, calcium, inositol trisphosphate, diacylglycerol, and fatty acids...
  35. PHOSPHOINOSITIDE HYDROLYSIS AND BETA CELL SECRETION
    Walter Zawalich; Fiscal Year: 1999
    ..b>Islets of Langerhans contain the three major isozymes of PLC(beta1, gamma1 and delta1) and the calcium- dependent PKC isozyme, ..
  36. HORMONES AND THE PROGRAMMED DEATH IN PETROMYZON MARINUS
    AUGUST EPPLE; Fiscal Year: 1980
    ..changes in the pituitary structure which require further analysis; (4) a continuous proliferation of the islets of Langerhans with the appearance of 3 new cell types in addition to the B-cells...
  37. STUDIES ON PANCREATIC HORMONES
    DONALD STEINER; Fiscal Year: 1991
    ..biological mechanisms underlying the production and actions of insulin and related peptide hormones of the islets of Langerhans, including their genetic basis, evolution origins and disorders which may contribute to the pathophysiology ..
  38. PANCREATIC HORMONES
    DONALD STEINER; Fiscal Year: 1990
    ..biological mechanisms underlying the production and actions of insulin and related peptide hormones of the islets of Langerhans, including their genetic basis, evolution origins and disorders which may contribute to the pathophysiology ..
  39. MICROENZYMATIC STUDIES OF ISLETS OF LANGERHANS
    Michael McDaniel; Fiscal Year: 1990
    ..Finally, the characterization and identification of a phosphoprotein intermediate localized to the endoplasmic reticulum Ca2+-ATPase will be performed to correlate further the Ca2+-ATPase with Ca2+ transport by this organelle...
  40. Gene transfer with A20 to improve islet transplantation
    Christiane Ferran; Fiscal Year: 2003
    ..the first series of successful islet transplantation in Edmonton Canada reestablished transplantation of islets of Langerhans as a viable therapeutic option for the cure of type I diabetes...
  41. Gene transfer with A20 to improve islet transplantation
    Christiane Ferran; Fiscal Year: 2002
    ..the first series of successful islet transplantation in Edmonton Canada reestablished transplantation of islets of Langerhans as a viable therapeutic option for the cure of type I diabetes...
  42. LYMPHOTOXIN AND LYMPHOID NEOGENESIS
    NANCY RUDDLE; Fiscal Year: 2004
    ..under the control of the rat insulin promoter (RIPLT mouse) that expresses LTalpha constitutively in the islets of Langerhans, the kidney, and skin, exhibit inflammation at the sites of transgene expression that has many ..
  43. LYMPHOTOXIN AND LYMPHOID NEOGENESIS
    NANCY RUDDLE; Fiscal Year: 2001
    ..under the control of the rat insulin promoter (RIPLT mouse) that expresses LTalpha constitutively in the islets of Langerhans, the kidney, and skin, exhibit inflammation at the sites of transgene expression that has many ..
  44. LYMPHOTOXIN AND LYMPHOID NEOGENESIS
    NANCY RUDDLE; Fiscal Year: 2003
    ..under the control of the rat insulin promoter (RIPLT mouse) that expresses LTalpha constitutively in the islets of Langerhans, the kidney, and skin, exhibit inflammation at the sites of transgene expression that has many ..
  45. SUBRETINAL TRANSPLANTATION OF ISLETS OF LANGERHANS
    Dennis Rickman; Fiscal Year: 2000
    ..Such control might be possible with pancreatic transplant or transplantation of isolated islets of Langerhans. Isolated islets of Langerhans, transplanted in an immune privileged site such as the testis, or with ..
  46. LYMPHOTOXIN AND LYMPHOID NEOGENESIS
    NANCY RUDDLE; Fiscal Year: 2000
    ..under the control of the rat insulin promoter (RIPLT mouse) that expresses LTalpha constitutively in the islets of Langerhans, the kidney, and skin, exhibit inflammation at the sites of transgene expression that has many ..
  47. IMMUNE MECHANISM FOR PREVENTING AUTOIMMUNE DIABETES
    Kevan Herold; Fiscal Year: 1992
    ..dependent diabetes mallitus (IDDM) is believed to represent the end stage of an autoimmune attack on the islets of Langerhans. Work in animal models of the disease has provided information related to the pathogenesis of the disease, ..
  48. SUBRETINAL TRANSPLANTATION OF ISLETS OF LANGERHANS
    Diane Hatchell; Fiscal Year: 1999
    ..Such control might be possible with pancreatic transplant or transplantation of isolated islets of Langerhans. Isolated islets of Langerhans, transplanted in an immune privileged site such as the testis, or with ..
  49. LYMPHOTOXIN AND LYMPHOID NEOGENESIS
    NANCY RUDDLE; Fiscal Year: 2002
    ..under the control of the rat insulin promoter (RIPLT mouse) that expresses LTalpha constitutively in the islets of Langerhans, the kidney, and skin, exhibit inflammation at the sites of transgene expression that has many ..
  50. Modulation of pancreatic endocrine function
    Brian Tobin; Fiscal Year: 2001
    ..We hypothesize that human pancreatic islets of Langerhans have an increased requirement for amino acids in microgravity...
  51. Real-Time Analyses of Apoptosis in Human Beta Cells
    Michael Roe; Fiscal Year: 2005
    ..Our preliminary experiments in MIN6 cells and in mouse islets of Langerhans indicate that ER stress induced by disruption of sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) activity ..
  52. Real-Time Analyses of Apoptosis in Human Beta Cells
    Michael Roe; Fiscal Year: 2004
    ..Our preliminary experiments in MIN6 cells and in mouse islets of Langerhans indicate that ER stress induced by disruption of sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) activity ..
  53. DYNORPHIN AND BETA CELL SENSITIZATION
    MARVIN GERSHENGORN; Fiscal Year: 1999
    ..opioid receptors, synergize with glucose to stimulate insulin secretion from beta cells of the pancreatic islets of Langerhans. The following hypothesis will be tested...
  54. 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...
  55. Antigens Recognized by CD8+ T Cells in Type 1 Diabetes
    Teresa Dilorenzo; Fiscal Year: 2006
    ..is an autoimmune disease resulting from destruction of the insulin-producing beta cells in the pancreatic islets of Langerhans. Insulin injections allow for continuation of life for the one million Americans afflicted with type 1 ..
  56. The role of innervation for hormone secretion in human islets
    ALEJANDRO CAICEDO VIERKANT; Fiscal Year: 2009
    There is a fundamental gap in understanding how the islets of Langerhans function in vivo, either in the native environment in the pancreas or after transplantation to treat type 1 diabetes...
  57. METABOLISM OF ISLETS OF LANGERHANS AND HORMONE RELEASE
    Franz Matschinsky; Fiscal Year: 1999
    ....
  58. METABOLISM OF ISLETS OF LANGERHANS AND HORMONE RELEASE
    Franz Matschinsky; Fiscal Year: 2001
    ....
  59. METABOLISM OF ISLETS OF LANGERHANS AND HORMONE RELEASE
    Franz Matschinsky; Fiscal Year: 2000
    ....
  60. METABOLISM OF ISLETS OF LANGERHANS AND HORMONE RELEASE
    Franz Matschinsky; Fiscal Year: 2002
    ....
  61. Molecular Phenotyping of NOD Mice
    Ivan Gerling; Fiscal Year: 2006
    ..In this competitive renewal application we propose to shift the focus from islets of Langerhans to lymphocytes. We will characterize lymphocytes in great details...
  62. Molecular Phenotyping of NOD Mice
    Ivan Gerling; Fiscal Year: 2007
    ..In this competitive renewal application we propose to shift the focus from islets of Langerhans to lymphocytes. We will characterize lymphocytes in great details...
  63. Molecular Phenotyping of NOD Mice
    Ivan Gerling; Fiscal Year: 2009
    ..In this competitive renewal application we propose to shift the focus from islets of Langerhans to lymphocytes. We will characterize lymphocytes in great details...
  64. Molecular Phenotyping of NOD Mice
    Ivan C Gerling; Fiscal Year: 2010
    ..In this competitive renewal application we propose to shift the focus from islets of Langerhans to lymphocytes. We will characterize lymphocytes in great details...
  65. Molecular Phenotyping of NOD Mice
    Ivan Gerling; Fiscal Year: 2007
    ..In this competitive renewal application we propose to shift the focus from islets of Langerhans to lymphocytes. We will characterize lymphocytes in great details...
  66. METABOLISM OF ISLETS OF LANGERHANS AND HORMONE RELEASE
    Franz Matschinsky; Fiscal Year: 2003
    ....
  67. METABOLISM OF ISLETS OF LANGERHANS AND HORMONE RELEASE
    Franz Matschinsky; Fiscal Year: 2006
    ....
  68. METABOLISM OF ISLETS OF LANGERHANS AND HORMONE RELEASE
    Franz Matschinsky; Fiscal Year: 2004
    ....
  69. METABOLISM OF ISLETS OF LANGERHANS AND HORMONE RELEASE
    Franz Matschinsky; Fiscal Year: 2005
    ....
  70. PHOSPHOINOSITIDE HYDROLYSIS AND BETA CELL SECRETION
    Walter Zawalich; Fiscal Year: 2000
    ..b>Islets of Langerhans contain the three major isozymes of PLC(beta1, gamma1 and delta1) and the calcium- dependent PKC isozyme, ..
  71. PHOSPHOINOSITIDE HYDROLYSIS AND BETA CELL SECRETION
    Walter Zawalich; Fiscal Year: 2002
    ..b>Islets of Langerhans contain the three major isozymes of PLC(beta1, gamma1 and delta1) and the calcium- dependent PKC isozyme, ..
  72. PHOSPHOINOSITIDE HYDROLYSIS AND BETA CELL SECRETION
    Walter Zawalich; Fiscal Year: 2001
    ..b>Islets of Langerhans contain the three major isozymes of PLC(beta1, gamma1 and delta1) and the calcium- dependent PKC isozyme, ..
  73. PREGNANCY: MECHANISM OF ITS EFFECT ON INSULIN RELEASE
    LOREN LIPSON; Fiscal Year: 1980
    ..study is to investigate the mechanism by which pregnancy alters the insulin secretory characteristics of islets of Langerhans. Specifically insulin release has been shown to be increased in response to glucose stimulation in the ..
  74. Pancreas Transporter Development and Validation
    Michael Taylor; Fiscal Year: 2005
    Transplantation of islets of Langerhans for the clinical treatment of Type I diabetes has had a resurgence of interest due to results obtained using the "Edmonton protocol"...
  75. Targeting SUMO proteases for type II diabetes
    Benjamin Nicholson; Fiscal Year: 2010
    ..The secretion of insulin from 2-cells in pancreatic islets of Langerhans is regulated by numerous ion channels leading to calcium-dependent insulin exocytosis...
  76. Wnt/beta-catenin signaling in exocrine pancreas developoment and regeneration
    LEWIS MURTAUGH; Fiscal Year: 2009
    ..The endocrine pancreas includes insulin-producing beta cells, resident in the islets of Langerhans, while the exocrine pancreas comprises digestive enzyme-secreting acinar cells andthe ducts through which ..
  77. T cell activation and repertoire in insulin dependent diabetes / anti CD40L trial
    Kevan Herold; Fiscal Year: 1999
    ..disease caused, in part, by a T cell mediated destruction of the insulin producing beta cells in the islets of Langerhans. Studies in animal models and limited human clinical studies demonstrate that modulation of T cell ..
  78. Wnt/beta-catenin signaling in exocrine pancreas developoment and regeneration
    LEWIS MURTAUGH; Fiscal Year: 2007
    ..The endocrine pancreas includes insulin-producing beta cells, resident in the islets of Langerhans, while the exocrine pancreas comprises digestive enzyme-secreting acinar cells and the ducts through which ..
  79. Epitenetic regulation and enhancement of beta cell differentiation
    Arthur D Riggs; Fiscal Year: 2010
    ..replacement therapy of type 1 diabetes, a disease in which insulin-secreting beta cells in the pancreatic islets of Langerhans are destroyed by autoimmunity...
  80. T cell activation and repertoire in insulin dependent diabetes / anti CD40L trial
    Kevan Herold; Fiscal Year: 2001
    ..disease caused, in part, by a T cell mediated destruction of the insulin producing beta cells in the islets of Langerhans. Studies in animal models and limited human clinical studies demonstrate that modulation of T cell ..