Objective: To investigate the apoptosis of isolated pancreatic islet cells and insulin secretion induced by combination of IL-1β

TNF and IFN-γ

and to investigate the mechanism of the change.Methods: Isolated pancreatic islet cells from Wistar rat were incubated in monolayer in vitro.NO production

NOS activity

insulin secretion

the protein expression of bcl-xl and bax

apoptotic rate of islet cells and DNA fragmentation in pancreatic islet cells incubated with combination of IL-1β

TNF and IFN-γ were measured.Results: Combination of IL-1β

TNF and IFN-γ induced a significant increase in apoptotic percentage of pancreatic islet cells

NO production and NOS activity

as well as DNA ladder appearance

while a decrease in insulin content.Up-regulation of the protein expression of bax and down-regulation of the protein expression of bcl-xl were also induced(P<0.01).These effects occurred in a time and dose dependent manner.Conclusion: The cytokines can induce β cell apoptosis

the mechanism of which may be the activation of NOS and the increase of NO production and the upregulation of bax/bcl-xl proportion.