The glycolipid sulfatide protects insulin-producing cells against cytokine-induced apoptosis, a possible role in diabetes

Aims/hypothesis Cytokine-induced apoptosis is recognised as a major cause of the decline in beta-cell mass that ultimately leads to type 1 diabetes mellitus. Interleukin-1 beta, interferon-gamma and tumour necrosis factor-alpha in conjunction initiate a series of events that lead to beta-cell apoptosis; important among these is NO production. The glycosphingolipid sulfatide is present in beta-cells in the secretory granules in varying amounts and is secreted together with insulin. We now investigate whether sulfatide is able to protect insulin-producing cells against the pro-apoptotic effect of interleukin-1 beta, interferon-gamma and tumour necrosis factor-alpha. Methods INS-1E cells and genuine rat islets were incubated for 24 h exposed to interleukin-1 beta, interferon-gamma and tumour necrosis factor-alpha with or without sulfatide. The production of NO was monitored and the number of apoptotic cells was determined using terminal deoxynucleotidyl transferase-mediated dUTP Nick-End labelling and caspase-3/7 activity assays. In addition, the amount of iNOS mRNA was determined using real-time quantitative polymerase chain reaction. Results Cytokine-induced apoptosis was reduced to 27% of cytokine-treated controls with 30 mu mol/L sulfatide treatment (p < 0.01). Likewise, sulfatide in concentrations of 3-30 mu mol/L decreased NO production in a dose-dependent manner to 19-40% of cytokine-treated controls (overall p = 0.0007). The level of iNOS mRNA after cytokine exposure was reduced to 55% of cytokine-treated controls with 30 mu mol/L of sulfatide. Conclusions/interpretation In the present study, we report the ability of sulfatide to significantly reduce apoptosis, cellular leakage and NO production in insulin-producing cells. Data suggest this is not due to induction of beta-cell rest. Our findings indicate a possible implication for sulfatide in the pathogenesis of diabetes. Copyright. (C) 2010 John Wiley & Sons, Ltd.