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 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
  2. 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
  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. pmc neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas
    G Gradwohl
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique Institut National de la Santé et de la Recherche Médicale Université Louis Pasteur, F 67404 Illkirch, France
    Proc Natl Acad Sci U S A 97:1607-11. 2000
  5. 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
  6. 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
  7. 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
  8. pmc Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets
    Kathrin Maedler
    Division of Endocrinology and Diabetes, University Hospital, Zurich, Switzerland
    J Clin Invest 110:851-60. 2002
  9. ncbi Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knock-outs using Cre recombinase
    C Postic
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Biol Chem 274:305-15. 1999
  10. ncbi p16INK4a induces an age-dependent decline in islet regenerative potential
    Janakiraman Krishnamurthy
    Department of Medicine, The Lineberger Comprehensive Cancer Center, The University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    Nature 443:453-7. 2006

Detail Information

Publications307 found, 100 shown here

  1. 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
    ....
  2. 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...
  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. pmc neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas
    G Gradwohl
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique Institut National de la Santé et de la Recherche Médicale Université Louis Pasteur, F 67404 Illkirch, France
    Proc Natl Acad Sci U S A 97:1607-11. 2000
    In the mammalian pancreas, the endocrine cell types of the islets of Langerhans, including the alpha-, beta-, delta-, and pancreatic polypeptide cells as well as the exocrine cells, derive from foregut endodermal progenitors...
  5. 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...
  6. 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
    ....
  7. 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...
  8. pmc Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets
    Kathrin Maedler
    Division of Endocrinology and Diabetes, University Hospital, Zurich, Switzerland
    J Clin Invest 110:851-60. 2002
    ..These findings implicate an inflammatory process in the pathogenesis of glucotoxicity in type 2 diabetes and identify the IL-1beta/NF-kappaB pathway as a target to preserve beta cell mass and function in this condition...
  9. ncbi Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knock-outs using Cre recombinase
    C Postic
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Biol Chem 274:305-15. 1999
    ..Interestingly, hepatic GK knock-out mice also have impaired insulin secretion in response to glucose. These studies indicate that deficiencies in both beta cell and hepatic GK contribute to the hyperglycemia of MODY-2...
  10. ncbi p16INK4a induces an age-dependent decline in islet regenerative potential
    Janakiraman Krishnamurthy
    Department of Medicine, The Lineberger Comprehensive Cancer Center, The University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    Nature 443:453-7. 2006
    ..These genetic data support the view that an age-induced increase of p16INK4a expression limits the regenerative capacity of beta-cells with ageing...
  11. 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
    ....
  12. 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...
  13. 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...
  14. ncbi Adult insulin- and glucagon-producing cells differentiate from two independent cell lineages
    P L Herrera
    Department of Morphology, University of Geneva Medical School, rue Michel Servet, Switzerland
    Development 127:2317-22. 2000
    ..Thus the islet alpha- and beta-cell lineages appear to arise independently during ontogeny, probably from a common precursor...
  15. 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...
  16. 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
    ....
  17. ncbi 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...
  18. 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...
  19. ncbi 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...
  20. ncbi Superoxide activates mitochondrial uncoupling proteins
    Karim S Echtay
    Medical Research Council Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 2XY, UK
    Nature 415:96-9. 2002
    ..Our findings indicate that the interaction of superoxide with UCPs may be a mechanism for decreasing the concentrations of reactive oxygen species inside mitochondria...
  21. pmc Gene expression profiling in single cells from the pancreatic islets of Langerhans reveals lognormal distribution of mRNA levels
    Martin Bengtsson
    Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden
    Genome Res 15:1388-92. 2005
    ..Hence, the geometric mean of expression levels provides a better estimate of gene activity of the typical cell than does the arithmetic mean measured on a cell population...
  22. 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...
  23. 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...
  24. ncbi Pancreatic islet production of vascular endothelial growth factor--a is essential for islet vascularization, revascularization, and function
    Marcela Brissova
    Division of Diabetes, Endocrinology, and Metabolism, 715 PRB, Vanderbilt University, Nashville, TN 37232, USA
    Diabetes 55:2974-85. 2006
    ..Factors modulating VEGF-A expression may influence islet vascularity and, consequently, the amount of insulin delivered into the systemic circulation...
  25. pmc The human pancreatic islet transcriptome: expression of candidate genes for type 1 diabetes and the impact of pro-inflammatory cytokines
    Decio L Eizirik
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles ULB, Brussels, Belgium
    PLoS Genet 8:e1002552. 2012
    ..have used RNA sequencing (RNA-seq) to identify transcripts, including splice variants, expressed in human islets of Langerhans under control conditions or following exposure to the pro-inflammatory cytokines interleukin-1β (IL-1β) ..
  26. ncbi Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes
    Anna L Gloyn
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom
    N Engl J Med 350:1838-49. 2004
    ..2 subunit of this channel (KCNJ11) cause neonatal diabetes...
  27. 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...
  28. ncbi The Pax4 gene is essential for differentiation of insulin-producing beta cells in the mammalian pancreas
    B Sosa-Pineda
    Max Planck Institute for Biophysical Chemistry, Gottingen, Germany
    Nature 386:399-402. 1997
    ..A default pathway would explain the elevated number of alpha cells in the absence of Pax4...
  29. 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...
  30. 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...
  31. 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...
  32. 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...
  33. 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...
  34. 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...
  35. 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...
  36. 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
    ....
  37. ncbi Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea
    Kun Ho Yoon
    Department of Endocrinology and Metabolism, Immunology, and Cell Biology Core Laboratory, Institutes of Medical Science, The Catholic University of Korea, Seoul, Korea 137 701
    J Clin Endocrinol Metab 88:2300-8. 2003
    ..Moreover, decreased beta-cell but increased alpha-cell proportion in the islets suggests for a selective beta-cell loss in the pathogenesis of Korean type 2 diabetes...
  38. 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...
  39. 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...
  40. ncbi Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation
    M Cnop
    Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium
    Diabetes 50:1771-7. 2001
    ..It is conceivable that this potential is lost or insufficient in cells with a prolonged triglyceride accumulation as may occur in vivo...
  41. pmc Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients
    G J Cooper
    Department of Biochemistry, University of Oxford, United Kingdom
    Proc Natl Acad Sci U S A 84:8628-32. 1987
    ..The accumulation of amyloid, including diabetes-associated peptide, in islets may impair islet function in type 2 diabetes mellitus...
  42. ncbi A genetic and physiological study of impaired glucose homeostasis control in C57BL/6J mice
    A A Toye
    Medical Research Council, Harwell, Didcot, Oxfordshire, UK
    Diabetologia 48:675-86. 2005
    ..C57BL/6J mice exhibit impaired glucose tolerance. The aims of this study were to map the genetic loci underlying this phenotype, to further characterise the physiological defects and to identify candidate genes...
  43. pmc How punctual ablation of regulatory T cells unleashes an autoimmune lesion within the pancreatic islets
    Markus Feuerer
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Immunity 31:654-64. 2009
    ..Thus, Treg cells regulate pancreatic autoimmunity in situ through control of a central innate immune system player, NK cells...
  44. ncbi 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...
  45. 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 ..
  46. 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...
  47. 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...
  48. pmc Bisphenol A exposure during pregnancy disrupts glucose homeostasis in mothers and adult male offspring
    Paloma Alonso-Magdalena
    Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM, Universidad Miguel Hernandez de Elche, Elche, Spain
    Environ Health Perspect 118:1243-50. 2010
    ..In humans, epidemiological evidence has associated BPA exposure in adults with higher risk of type 2 diabetes and heart disease...
  49. 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...
  50. pmc Cellular and molecular events in the localization of diabetogenic T cells to islets of Langerhans
    Boris Calderon
    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 108:1561-6. 2011
    ..Here, the events that lead to specific localization of diabetogenic CD4 T cells into islets of Langerhans resulting in diabetes were examined...
  51. pmc Intravital imaging of CTLs killing islet cells in diabetic mice
    Ken Coppieters
    Type 1 Diabetes Center, The La Jolla Institute for Allergy and Immunology, La Jolla, California, USA
    J Clin Invest 122:119-31. 2012
    ..Collectively, these data portray the kinetics of CTL homing to and between antigenic target sites as a stochastic process at the sub-organ level and argue against a dominant influence of chemotactic gradients...
  52. pmc Maternal diet and aging alter the epigenetic control of a promoter-enhancer interaction at the Hnf4a gene in rat pancreatic islets
    Ionel Sandovici
    Metabolic Research Laboratories, Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge CB2 0SW, United Kingdom
    Proc Natl Acad Sci U S A 108:5449-54. 2011
    ..We therefore propose that environmentally induced changes in promoter-enhancer interactions represent a fundamental epigenetic mechanism by which nutrition and aging can influence long-term health...
  53. 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...
  54. 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...
  55. 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...
  56. pmc IL-1beta receptor blockade protects islets against pro-inflammatory cytokine induced necrosis and apoptosis
    Alice Schwarznau
    Department of Surgery, Technical University of Munich, Munich, Germany
    J Cell Physiol 220:341-7. 2009
    ....
  57. 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...
  58. 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...
  59. ncbi 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...
  60. 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...
  61. ncbi Free fatty acid receptor 1 (FFA(1)R/GPR40) and its involvement in fatty-acid-stimulated insulin secretion
    A Salehi
    Section of Diabetes and Endocrinology, BMC B11, 22184 Lund, Sweden
    Cell Tissue Res 322:207-15. 2005
    ..The results demonstrate that FFA(1)R/GPR40 is inhibited by the CPT-1 inhibitor, 2BrP, and confirm that FFA(1)R/GPR40 is indeed necessary, at least in part, for fatty-acid-stimulated insulin release...
  62. pmc IL-1 antagonism reduces hyperglycemia and tissue inflammation in the type 2 diabetic GK rat
    J A Ehses
    Division of Endocrinology, Diabetes, and Nutrition and Center for Integrated Human Physiology, University Hospital of Zurich, 8045 Zurich, Switzerland
    Proc Natl Acad Sci U S A 106:13998-4003. 2009
    ..Rather than being directly cytotoxic, IL-1beta may drive tissue inflammation that impacts on both beta cell functional mass and insulin sensitivity in type 2 diabetes...
  63. 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...
  64. 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...
  65. 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...
  66. ncbi Distinct effects of saturated and monounsaturated fatty acids on beta-cell turnover and function
    K Maedler
    Division of Endocrinology and Diabetes, University Hospital, Zurich, Switzerland
    Diabetes 50:69-76. 2001
    ....
  67. 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...
  68. 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
  69. pmc Nitric oxide-induced apoptosis in pancreatic beta cells is mediated by the endoplasmic reticulum stress pathway
    S Oyadomari
    Department of Molecular Genetics, Kumamoto University School of Medicine, Honjo 2 2 1, Kumamoto 860 0811, Japan
    Proc Natl Acad Sci U S A 98:10845-50. 2001
    ..We conclude that NO depletes ER Ca(2+), causes ER stress, and leads to apoptosis. Thus, ER Ca(2+) stores are a new target of NO, and the ER stress pathway is a major mechanism of NO-mediated beta cell apoptosis...
  70. 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...
  71. ncbi Evidence that oestrogen receptor-alpha plays an important role in the regulation of glucose homeostasis in mice: insulin sensitivity in the liver
    G Bryzgalova
    Department of Molecular Medicine, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden
    Diabetologia 49:588-97. 2006
    ..We used oestrogen receptor-alpha (ERalpha) knockout (ERKO) and receptor-beta (ERbeta) knockout (BERKO) mice to investigate the mechanism(s) behind the effects of oestrogens on glucose homeostasis...
  72. 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...
  73. ncbi Transgenic mice with green fluorescent protein-labeled pancreatic beta -cells
    Manami Hara
    Department of Medicine, The University of Chicago, Illinois 60637, USA
    Am J Physiol Endocrinol Metab 284:E177-83. 2003
    ..4 +/- 0.2% (n = 6) of the cells in the pancreas of newborn (P1) and 0.9 +/- 0.1% (n = 5) of 8-wk-old mice were beta-cells. The MIP-GFP-transgenic mouse may be a useful tool for studying beta-cell biology in normal and diabetic animals...
  74. 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...
  75. ncbi Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of beta-cell formation in the pancreas
    M Sander
    Hormone Research Institute, University of California San Francisco, San Francisco, CA 94143 0534, USA
    Development 127:5533-40. 2000
    ..Together, these experiments reveal two independently controlled pathways for beta-cell differentiation, and place Nkx6.1 downstream of Nkx2.2 in the major pathway of beta-cell differentiation...
  76. pmc Global epigenomic analysis of primary human pancreatic islets provides insights into type 2 diabetes susceptibility loci
    Michael L Stitzel
    Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Cell Metab 12:443-55. 2010
    ..These findings present a global snapshot of the human islet epigenome and should provide functional context for noncoding variants emerging from genetic studies of T2D and other islet disorders...
  77. 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...
  78. 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...
  79. 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...
  80. 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...
  81. 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...
  82. 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
    ....
  83. 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
    ....
  84. 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
    ....
  85. 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...
  86. 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...
  87. ncbi 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...
  88. 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 ..
  89. 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...
  90. 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.
  91. 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...
  92. ncbi 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...
  93. 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...
  94. 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...
  95. 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...
  96. 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...
  97. 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...
  98. 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...
  99. 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)...
  100. 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...
  101. 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...

Research Grants63

  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 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 ..
  3. METABOLIC REGULATION IN THE ACUTE PHASE
    HYUNG D RYOO; Fiscal Year: 2010
    ..stress is also likely to occur in secretory cells handling heavy client protein loads, such as 13cells in islets of Langerhans in insulin resistant humans...
  4. Modulation of beta-cell PKA activity affects glucose homeostasis
    Barton Wicksteed; Fiscal Year: 2013
    ..shows considerable potential in treating diabetes by preserving the ability of the beta-cells of the islets of Langerhans to secrete insulin and in patenting beta-cell mass...
  5. 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...
  6. From destructive to protective: altering the fate of a diabetogenic T cell using
    JENNIFER DIANNA HOOD; Fiscal Year: 2012
    ..mediated by CD4 T cells that leads to the destruction of the insulin producing beta cells in the pancreatic islets of Langerhans. Once the beta cells are destroyed, blood sugar levels are unable to be controlled due to the lack of ..
  7. MOLECULAR BASIS OF ANTIDIABETOGENIC HORMONE ACTION
    George G Holz; Fiscal Year: 2010
    ..in part, from its ability to stimulate the secretion of insulin from pancreatic beta cells located in the islets of Langerhans. Given the established importance of GLP-1 for the treatment of diabetes, our laboratory is interested in ..
  8. Epitenetic regulation and enhancement of beta cell differentiation
    Arthur D Riggs; Fiscal Year: 2011
    ..replacement therapy of type 1 diabetes, a disease in which insulin-secreting beta cells in the pancreatic islets of Langerhans are destroyed by autoimmunity...
  9. The role of innervation for hormone secretion in human islets
    ALEJANDRO CAICEDO VIERKANT; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): 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...
  10. Nkx2.2 in Pancreatic Development: The Role of the NK2-SD Domain
    JOSHUA ADAM LEVINE; Fiscal Year: 2013
    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 ...
  11. 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...
  12. Role of chemokines in diabetes
    Sergio A Lira; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Recruitment of leukocytes into the pancreatic islets of Langerhans is a necessary step in the pathogenesis of Type I diabetes...
  13. Development of Human beta cell-specific AAV Vectors for Type I Diabetes
    Roland M Tisch; Fiscal Year: 2013
    ..is characterized by the autoimmune-mediated destruction of the insulin producing [unreadable] cells of the islets of Langerhans. Our work and that of others in murine models has shown that transferring genes for immunoregulatory ..
  14. 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...
  15. The Ldb1 coregulator controls LIM target genes in developing and adult islets.
    Chad S Hunter; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Pancreatic beta cells within the Islets of Langerhans are required for glucose-stimulated insulin secretion and glucose homeostasis...
  16. Microfluidic devices for determining dynamics of islets of Langerhans
    MICHAEL GABRIEL ROPER; Fiscal Year: 2013
    ..Ultimately, such knowledge has the potential to guide the development of therapeutics for reducing the problems associated with glucose toxicity in type II diabetics. ..
  17. Multipotent mesenchymal stem cell-like cells in pancreatic tumorigenesis
    NADEZDA ALEKSANDROVNA ISACHENKO; Fiscal Year: 2012
    ..it develops pancreatic islet cell carcinomas in a multi-step pathway arising from normal beta cells in the islets of Langerhans through two distinct premalignant stages to highly vascularized large adenomas and invasive carcinomas...
  18. The role of EphA-ephrin-A signaling in glucose-inhibition of glucagon secretion
    Troy Hutchens; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The islets of Langerhans play a central role in blood glucose homeostasis through glucose regulated dose-dependent hormone secretion...
  19. A Novel Approach of beta Cell Replacement to Reverse Type I Diabetes in NOD Mice
    Roland M Tisch; Fiscal Year: 2013
    ..an autoimmune disease characterized by the destruction of the insulin producing beta cells residing in the islets of Langerhans. In order to provide a "cure" for chronic diabetic individuals the beta cell mass that has been destroyed ..
  20. 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"...
  21. Mechanisms of Viral-Induced Beta Cell Damage
    John A Corbett; Fiscal Year: 2012
    ..disease that is characterized by selective destruction of insulin secreting beta-cells found in pancreatic islets of Langerhans. Viral infection is one event proposed to initiate beta-cell damage during the development of this disease...
  22. Molecular Physiology of Store-Dependant Calcium Entry in Pancreatic Beta Cells.
    MICHAEL WILLIAM ROE; Fiscal Year: 2013
    ..Preliminary evidence also suggests that store-operated Ca2+ entry (SOCE) is abnormal in islets of Langerhans isolated from a mouse model of T2DM...
  23. DESIGN AND USE OF METHODS FOR PEPTIDE SECRETION STUDIES
    Robert T Kennedy; Fiscal Year: 2013
    A hallmark of Type 2 diabetes is impaired insulin secretion from beta cells of the islets of Langerhans. Greater understanding of islets and insulin secretion is of fundamental importance in determining the root causes of diabetes and ..
  24. Quantitative analysis of aging in the human pancreas
    Manami Hara; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The islets of Langerhans which are distributed throughout the pancreas comprise 1-2% of the mass of the pancreas and contain the endocrine cells that secrete insulin (beta-cells) and other hormones...
  25. Magnetic Flow Sorter for Pancreatic Islet Isolation
    Paul W Todd; Fiscal Year: 2013
    ..successfully completed SBIR Phase I and Phase II research demonstrating that magnetically labeled porcine islets of Langerhans can be isolated from contaminating exocrine tissue by flow sorting using a quadrupole magnetic separator ("..
  26. 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...
  27. 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...
  28. 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...
  29. 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...
  30. 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...
  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. 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...
  33. 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...
  34. Targeting CD8+ T Cell to Prevent B Cell Destruction
    JEFFREY ALLEN FRELINGER; Fiscal Year: 2010
    ..autoimmune disease characterized by the T mediated destruction of the insulin producing b cells of the islets of Langerhans. Treatment of diabetes has focused on the use of insulin replacement...
  35. 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...
  36. 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 ..
  37. 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...
  38. 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...
  39. 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...
  40. 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...
  41. 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 ..
  42. PATHOGENESIS OF TYPE I DIABETES IN MONOZYGOTIC TWINS
    JOHN SOELDNER; Fiscal Year: 1991
    ..mechanisms, possible etiologic agent(s) and the natural history of the interplay of autoimmunity and the islets of Langerhans, as it relates to the pathogenesis of insulin dependent diabetes (IDDM)...
  43. Ultrasonic Measurement of Islet Volume
    STEVEN AFRICK; Fiscal Year: 2005
    ..of this project is to develop a novel in vitro technique for measurement of total cell volume in samples of islets of Langerhans that will be useful for assessing the quality of islet preparations for pancreatic transplantation and ..
  44. Does insulin or glucose regulate alpha-cell function?
    Barton Wicksteed; Fiscal Year: 2006
    ..range, primarily due to insulin and glucagon, which are secreted from the beta and alpha cells of the islets of Langerhans, respectively...
  45. DNA Immunizations with GAD65 to Induce Tolerance
    PENELOPE MOREL; Fiscal Year: 2002
    ..an autoimmune disease characterized by T cell- mediated destruction of the insulin-producing cells of the islets of Langerhans. The murine model of insulin dependent diabetes mellitus (IDDM), the non-obese diabetic (NOD) mouse has ..
  46. Hydroxamate-based therapy to target T cell homing in IDDM
    Alex Strongin; Fiscal Year: 2007
    ..is essential for both efficient adhesion and for transendothelial migration of T killer cells into the islets of Langerhans. After penetration into the islets, cytotoxic T cells cause the destruction of insulin-producing p cells...
  47. Regulation of IDDM by AIM and Th1-cytokines
    Toru Miyazaki; Fiscal Year: 2003
    Insulin-dependent diabetes mellitus (IDDM) is characterized by the infiltration of T-lymphocytes into the islets of Langerhans of the pancreas (insulitis), followed by selective destruction of insulin-secreting beta-cells leading to overt ..
  48. The Role of IL-2 in Autoimmune Diabetes
    Richard Flavell; Fiscal Year: 2007
    Type 1 insulin-dependent diabetes mellitus is caused by an autoimmune attack on the islets of Langerhans. The susceptibility to this disease is determined both genetically and by environmental events...
  49. INDUCTION OF TOLERANCE TO ISLET ALLOGRAFTS IN PRIMATES
    Lakshmi Gaur; Fiscal Year: 2000
    ..Both pancreas and islets of Langerhans have been transplanted successfully in humans and in animals models resulting in full normalization of ..
  50. Methods for Improving Pancreatic Islet Transplantation
    Stephen Navran; Fiscal Year: 2004
    Transplantation of islets of Langerhans has long held promise as a cure for Type 1 diabetes mellitus. In the past, most islet transplants failed to achieve insulin independence...
  51. 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...
  52. IMMUNOREGULATION OF IDDM
    Andrea Sant; Fiscal Year: 1999
    ..this Program Project is to develop means of preventing the immunologic destruction of the beta cells in the islets of Langerhans that leads to insulin dependent diabetes mellitus (IDDM)...
  53. ADAPTATION OF ISLETS OF LANGERHANS TO PREGNANCY
    ROBERT SORENSON; Fiscal Year: 2006
    ..Understanding the regulation of beta-cell glucose sensitivity is critical for understanding the progression of events that lead to gestational and type Il diabetes. ..
  54. GABA-B Receptors as Regulators of Islet Biology
    Kathleen Dunlap; Fiscal Year: 2003
    The failure of pancreatic islets of Langerhans to supply insulin in sufficient quantities to maintain blood glucose within physiological limits underlies Type 1 (insulin-dependent) and Type 2 (insulin-independent) diabetes mellitus...
  55. Beta-Cell Mass And Function In Implants and Pancreas
    Wen Hong Li; Fiscal Year: 2003
    Beta-cells of the islets of Langerhans play important roles in regulating metabolism through the action of secreting insulin. In type 1diabetes, beta cells are quickly damaged or destroyed...
  56. Role of ER Stress in Beta Cell Apoptosis
    Michael Roe; Fiscal Year: 2004
    ..ER) stress induced by disruption of ER Ca2+ homeostasis causes apoptosis in MIN6 cells and in mouse islets of Langerhans. The molecular signals linking ER stress and a-cell death are unresolved...
  57. Mechanism of PANDER Induced Apoptosis
    BRANT ROGER BURKHARDT; Fiscal Year: 2010
    ..PANDER message is dominantly expressed in the islets of Langerhans of the pancreas, and to a lesser extent in the small intestine and prostate...
  58. DEVELOPMENT OF NOVEL PANCREATIC BETA CELL MODELS
    PATRICIA HINKLE; Fiscal Year: 1999
    DESCRIPTION (taken from the application) Insulin production in the islets of Langerhans is regulated by Multiple hormonal, neuronal and paracrine factors acting through interconnected signal transduction pathways...
  59. Towards Understanding Islet Biology
    Lydia Aguilar Bryan; Fiscal Year: 2005
    The past decade has seen a burgeoning of interest in the biology of the pancreatic islets of Langerhans. The surge in activity is driven in large measure by the rapid increase in the incidence of diabetes, and the critical role of failure ..
  60. Transcriptional Regulation of Beta-Cell-Specific Expression of the MafA Gene
    CHAD HUNTER; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): The beta cells within the pancreatic islets of Langerhans are solely responsible for secreting insulin for maintaining proper glucose homeostasis...
  61. DESIGN AND USE OF METHODS FOR PEPTIDE SECRETION STUDIES
    Robert Kennedy; Fiscal Year: 2005
    ..These cells are found in small clusters of approximately 2000 cells known as islets of Langerhans. In most forms of type 2 diabetes, the defects leading to impaired insulin secretion are unknown...
  62. METABOLIC REGULATION OF BETA-CELL GENE EXPRESSION
    Michael German; Fiscal Year: 2000
    ..to determine how glucose and other nutrients regulate gene expression in the beta-cells of the pancreatic islets of langerhans and to apply this knowledge to understanding the pathophysiology of NIDDM...
  63. PATTERNING OF THE DEVELOPING ENDROCRINE PANCREAS
    Michael German; Fiscal Year: 2002
    ..the molecular mechanisms underlying the formation of the insulin-producing Beta-cells in the pancreatic islets of Langerhans and to apply this knowledge to the replacement of the absent or defective Beta-cells in patients with ..