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