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

Gene Ther. 2000 Dec;7(23):2015-22. doi: 10.1038/


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics
  • Analysis of Variance
  • Apoptosis
  • Cells, Cultured
  • Diabetes Mellitus, Type 1 / therapy*
  • Gene Expression
  • Genetic Therapy / methods*
  • Genetic Vectors / pharmacology
  • Glucose / pharmacology
  • Green Fluorescent Proteins
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Like Growth Factor I / genetics*
  • Insulin-Like Growth Factor I / metabolism
  • Interleukin-1 / physiology
  • Islets of Langerhans / metabolism*
  • Luminescent Proteins / genetics
  • Nitric Oxide / physiology
  • Transfection / methods*
  • beta-Galactosidase / genetics


  • Insulin
  • Interleukin-1
  • Luminescent Proteins
  • Green Fluorescent Proteins
  • Nitric Oxide
  • Insulin-Like Growth Factor I
  • beta-Galactosidase
  • Glucose