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Horm Metab Res 2009; 41(3): 207-212
DOI: 10.1055/s-0028-1093343
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Impact of Cytokine- and FasL-induced Apoptosis in the β-Cell Line NIT-1

P. Augstein 1 , P. Heinke 1 , C. Schober 2 , E. Salzsieder 1
  • 1Institute of Diabetes “Gerhardt Katsch” Karlsburg e.V., Karlsburg, Germany
  • 2Klinikum Südstadt, Rostock, Germany
Further Information

Publication History

received 16.04.2008

accepted 20.08.2008

Publication Date:
29 October 2008 (online)

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Abstract

Cytokine- and FasL-induced pathways contribute to β-cell death in type 1 diabetes. It remains unclear, however, whether pro-apoptotic cyto-kines or FasL have more apoptotic impact. Cytokine- and FasL-induced apoptosis were simulated using IL-1β/IFN-γ, Super-FasLigand and the β-cell line NIT-1. The role of caspases was addressed using the general caspase inhibitor ZVAD. Exposure to IL-1β/IFN-γ induced NIT-1 cell death. FasL augmented cytokine-induced cell death accompanied by increased caspase-3 activation, DNA fragmentation, and chromatin condensation. However, FasL mediated comparable effects on the mitochondrial transmembrane potential (Δψm) and nitrite in cytokine- and untreated cells. The cytokine-induced sequence of apoptotic events was (1) Fas, nitrite, (2) Δψm, (3) DNA fragmentation, cell death, and (4) chromatin condensation. In the presence of FasL, cell death and chromatin condensation appeared earlier implicating a compression of the apoptotic time course. General caspase inhibition using ZVAD prevented cell death, Δψm, and DNA fragmentation; however, Fas expression and nitrite were increased. In conclusion, cytokines account for the major part of cell death induced by the simultaneously action of FasL + IL-1β/IFN-γ. Caspases are of central importance for β-cell death.

Key words

type 1 diabetes - pancreatic β cell - cytokine-induced apoptosis - FasL-induced apoptosis

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Correspondence

P. AugsteinPhD 

Institute of Diabetes “Gerhardt Katsch” Karlsburg e.V.

Greifswalder Str.11e

17495 Karlsburg

Germany

Phone: +49/38355/68 40 0

Fax: +49/38355/68 44 4

Email: augstein@diabetes-karlsburg.de

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