Glucagon-like peptide-1 reverses the cytokines-induced expression of programmed cell death 5 gene in pancreatic ?-cells / 中国糖尿病杂志

ABSTRACT

Objective To investigate the effects of glucagon-like peptide-1(GLP-1)on the expression of apoptosis-related molecules including programmed cell death 5(PDCD-5)gene in pancreatic ? cells induced by proinflammatory cytokines.Methods Mouse islet ?-cell line NIT-1 was incubated for 24 h with cytokine mixture(Mix)in the absence or presence of GLP-1.The apoptotic cells were assayed by flow cytometry after stained with annexin V-FITC and propidium iodide(PI).The expressions of PDCD5,Fas,and caspase 3 were detected using reverse transcription-polymerase chain reaction(RT-PCR)and Western blot.Results The number of both annexin V single positive cells and annexin V/PI double positive cells significantly increased in the cells treated with 30 U/mL interleukin-1?(IL-1?)+ 100 U/mL interferon-?(IFN-?)+ 100 U/mL tumor necrosis factor-?(TNF-?).The expressions of PDCD5,Fas,and caspase 3 at both mRNA and protein levels were upregulated in the cells exposed to the cytokines.The above-mentioned effects of the cytokines were reversed by 10 nmol/L of GLP-1.Conclusion These data show that the proinflammatory cytokines cause pancreatic ? cell apoptosis via activation of PDCD5 signal pathway and that GLP-1 inhibits the upregulation of PDCD5 expression and the subsequent event of apoptosis induced by the cytokines.