Titre du document / Document title

Adenoviral vector-mediated insulin gene transfer in the mouse pancreas corrects streptozotocin-induced hyperglycemia

Auteur(s) / Author(s)

SHIFRIN A. L. ⁽¹⁾ ; AURICCHIO A. ⁽²⁾ ; YU Q-C ⁽²⁾ ; WILSON J. ⁽³⁾ ; RAPER S. E. ⁽⁴⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA, ETATS-UNIS
⁽²⁾ Institute for Human Gene Therapy, University of Pennsylvania School of Medicine, Philadelphia, PA, ETATS-UNIS
⁽³⁾ Institute for Human Gene Therapy, Department of Molecular and Cellular Engineering, Philadelphia, PA, ETATS-UNIS
⁽⁴⁾ Department of Surgery and Institute for Human Gene Therapy, University of Pennsylvania School of Medicine, Philadelphia, PA, ETATS-UNIS

Résumé / Abstract

Therapy for type 1 diabetes consists of tight blood glucose (BG) control to minimize complications. Current treatment relies on multiple insulin injections or an insulin pump placement, β-cell or whole pancreas transplantation. All approaches have significant limitations and have led to the realization that novel treatment strategies are needed. Pancreatic acinar cells have features that make them a good target for insulin gene transfer. They are not subject to autoimmune attack, a problem with pancreas or islets transplantation, they are avidly transduced by recombinant adenoviral vectors, and capable of exporting a variety of peptides into the portal circulation. Recombinant adenoviral vectors were engineered to express either wild-type or furin-modified human insulin cDNA (AdCMVhInsM). Immunodeficient mice were made diabetic with streptozotocin and injected intrapancreatically with the vectors. BG and blood insulin levels have normalized after administration of AdCMVhInsM. Immunohistochemistry and electron microscopy showed the presence of insulin in acinar cells throughout the pancreas and localization of insulin molecules to acinar cell vesicles. The data clearly establish a relationship between intrapancreatic vector administration, decreased BG and elevated blood insulin levels. The findings support the use of pancreatic acinar cells to express and secrete insulin into the blood stream.

Revue / Journal Title

Gene therapy   ISSN 0969-7128 

Source / Source

2001, vol. 8, n^o19, pp. 1480-1489 (72 ref.)

Langue / Language

Anglais

Editeur / Publisher

Nature Publishing Group, Basingstoke, ROYAUME-UNI  (1994) (Revue)

Mots-clés anglais / English Keywords

Autoimmune disease ; Immunopathology ; Endocrinopathy ; Enzyme ; Hydrolases ; Peptidases ; Serine endopeptidases ; Virus ; Vertebrata ; Mammalia ; Rodentia ; Gene therapy ; Insulin dependent diabetes ; Genetic transfer ; Furin ; Recombinant protein ; Insulin ; Human ; Route of administration ; Transduction ; Animal model ; Adenoviridae ; Mouse ;

Mots-clés français / French Keywords

Maladie autoimmune ; Immunopathologie ; Endocrinopathie ; Enzyme ; Hydrolases ; Peptidases ; Serine endopeptidases ; Virus ; Vertebrata ; Mammalia ; Rodentia ; Voie intrapancréatique ; Thérapie génique ; Diabète insulinodépendant ; Transfert génétique ; Furin ; Protéine recombinante ; Insuline ; Homme ; Voie administration ; Transduction ; Modèle animal ; Adenoviridae ; Souris ;

Mots-clés espagnols / Spanish Keywords

Enfermedad autoinmune ; Inmunopatología ; Endocrinopatía ; Enzima ; Hydrolases ; Peptidases ; Serine endopeptidases ; Virus ; Vertebrata ; Mammalia ; Rodentia ; Terapia génica ; Diabetes insulinodependiente ; Transferencia genética ; Furin ; Proteína recombinante ; Insulina ; Hombre ; Vía administración ; Transducción ; Modelo animal ; Adenoviridae ; Ratón ;

Localisation / Location

INIST-CNRS, Cote INIST : 26274, 35400009959322.0060