The glycolipid sulfatide protects insulin-producing cells against cytokine-induced apoptosis, a possible role in diabetes
✍ Scribed by A. Roeske-Nielsen; L. T. Dalgaard; J.-E. Månsson; K. Buschard
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 252 KB
- Volume
- 26
- Category
- Article
- ISSN
- 1520-7552
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✦ Synopsis
Abstract
Aims/hypothesis
Cytokine‐induced apoptosis is recognised as a major cause of the decline in β‐cell mass that ultimately leads to type 1 diabetes mellitus. Interleukin‐1β, interferon‐γ and tumour necrosis factor‐α in conjunction initiate a series of events that lead to β‐cell apoptosis; important among these is NO production. The glycosphingolipid sulfatide is present in β‐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‐1β, interferon‐γ and tumour necrosis factor‐α.
Methods
INS‐1E cells and genuine rat islets were incubated for 24 h exposed to interleukin‐1β, interferon‐γ and tumour necrosis factor‐α 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 µmol/L sulfatide treatment (p < 0.01). Likewise, sulfatide in concentrations of 3–30 µmol/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 µmol/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 β‐cell rest. Our findings indicate a possible implication for sulfatide in the pathogenesis of diabetes. Copyright © 2010 John Wiley & Sons, Ltd.