The glycolipid sulfatide protects insulin-producing cells against cytokine-induced apoptosis, a possible role in diabetes.
Diabetes Metab Res Rev
; 26(8): 631-8, 2010 Nov.
Article
en En
| MEDLINE
| ID: mdl-20886661
ABSTRACT
AIMS/HYPOTHESIS:
Cytokine-induced apoptosis is recognised as a major cause of the decline in ß-cell mass that ultimately leads to type 1 diabetes mellitus. Interleukin-1ß, interferon-γ and tumour necrosis factor-α in conjunction initiate a series of events that lead to ß-cell apoptosis; important among these is NO production. The glycosphingolipid sulfatide is present in ß-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-1ß, interferon-γ and tumour necrosis factor-α.METHODS:
INS-1E cells and genuine rat islets were incubated for 24 h exposed to interleukin-1ß, 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 ß-cell rest. Our findings indicate a possible implication for sulfatide in the pathogenesis of diabetes.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Sulfoglicoesfingolípidos
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Citocinas
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Apoptosis
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Diabetes Mellitus Tipo 2
/
Células Secretoras de Insulina
Límite:
Animals
Idioma:
En
Revista:
Diabetes Metab Res Rev
Asunto de la revista:
ENDOCRINOLOGIA
/
METABOLISMO
Año:
2010
Tipo del documento:
Article
País de afiliación:
Dinamarca