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Prevention of beta cell dysfunction and apoptosis activation in human islets by adenoviral gene transfer of the insulin-like growth factor i

Academic Article
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Overview

authors

  • Giannoukakis, N.
  • Mi, Z.
  • Rudert, W. A.
  • Gambotto, A.
  • Trucco, M.
  • Robbins, Paul D.

publication date

  • December 2000

journal

  • Gene Therapy  Journal

abstract

  • Interleukin-1beta is a potent pro-inflammatory cytokine that has been shown to inhibit islet beta cell function as well as to activate Fas-mediated apoptosis in a nitric oxide-dependent manner. Furthermore, this cytokine is effective in recruiting lymphocytes that mediate beta cell destruction in IDDM onset. The insulin-like growth factor I (IGF-I) has been shown to block IL-1beta actions in vitro. We hypothesized that gene transfer of the insulin-like growth factor I to intact human islets could prevent IL-1beta-induced beta cell dysfunction and sensitization to Fas-triggered apoptosis activation. Intact human islets were infected with adenoviral vectors encoding IGF-I as well as beta-galactosidase and enhanced green fluorescent protein as controls. Adenoviral gene transfer of human IGF-I prevented IL-1beta-mediated nitric oxide production from human islets in vitro as well as the suppression of beta cell function as determined by glucose-stimulated insulin production. Moreover, IGF-I gene transfer prevented IL-1beta-induced, Fas-mediated apoptosis. These results suggest that locally produced IGF-I from cultured islets may be beneficial in maintaining beta cell function and promoting islet survival before and following islet transplantation as a potential therapy for type I diabetes.

subject areas

  • Adenoviridae
  • Analysis of Variance
  • Apoptosis
  • Cells, Cultured
  • Diabetes Mellitus, Type 1
  • Gene Expression
  • Genetic Therapy
  • Genetic Vectors
  • Glucose
  • Green Fluorescent Proteins
  • Humans
  • Insulin
  • Insulin-Like Growth Factor I
  • Interleukin-1
  • Islets of Langerhans
  • Luminescent Proteins
  • Nitric Oxide
  • Transfection
  • beta-Galactosidase
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Research

keywords

  • IGF-I
  • IL-1 beta
  • adenovirus
  • gene therapy
  • islets
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Identity

International Standard Serial Number (ISSN)

  • 0969-7128

Digital Object Identifier (DOI)

  • 10.1038/sj.gt.3301333

PubMed ID

  • 11175313
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Additional Document Info

start page

  • 2015

end page

  • 2022

volume

  • 7

issue

  • 23

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