| The glycolipid sulfatide protects insulin-producing cells against cytokine-induced apoptosis, a possible role in diabetes. | |
| | |
MedLine Citation:
|
PMID: 20886661 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
A Roeske-Nielsen; L T Dalgaard; J-E Månsson; K Buschard |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-30 |
Journal Detail:
|
Title: Diabetes/metabolism research and reviews Volume: 26 ISSN: 1520-7560 ISO Abbreviation: Diabetes Metab. Res. Rev. Publication Date: 2010 Nov |
Date Detail:
|
Created Date: 2010-11-02 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 100883450 Medline TA: Diabetes Metab Res Rev Country: England |
Other Details:
|
Languages: eng Pagination: 631-8 Citation Subset: IM |
Copyright Information:
|
Copyright © 2010 John Wiley & Sons, Ltd. |
Affiliation:
|
Bartholin Institute, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark. allan@roeske.dk |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Factors of risk and maintenance for eating disorders: psychometric exploration of the cross-cultural...
Next Document: Postoperative myocardial injury after major head and neck cancer surgery.