RX871024 reduces NO production but does not protect against pancreatic β-cell death induced by proinflammatory cytokines

Irina I. Zaitseva, Vladimir Sharoyko, Joachim Størling, Suad Efendic, Christopher Guerin, Thomas Mandrup-Poulsen, Pierluigi Nicotera, Per Olof Berggren, Sergei V. Zaitsev

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The imidazoline compound RX871024 reduces IL-1β-induced NO production thereby protecting against IL-1β-induced β-cell apoptosis. The aim of this study was to evaluate whether imidazolines RX871024 and efaroxan protect β-cells against death in the presence of a combination of the cytokines IL-1β, IFNγ, and TNFα. To address this issue, experiments involving different methods for detection of cell death, different concentrations of the cytokines, and a variety of conditions of preparation and culturing of ob/ob mouse islets and β-cells have been carried out. Thoroughly performed experiments have not been able to demonstrate a protective effect of RX871024 and efaroxan on β-cell death induced by the combination of cytokines. However, the inhibitory effect of RX871024 on NO production in ob/ob mouse islets and β-cells was still observed in the presence of all three cytokines and correlated with the decrease in p38 MAPK phosphorylation. Conversely, efaroxan did not affect cytokine-induced NO production. Our data indicate that a combination of pro-inflammatory cytokines IL-1β, IFNγ, and TNFα, conditions modelling those that take place in type 1 diabetes, induces pancreatic β-cell death that does not directly correlate with NO production and cannot be counteracted with imidazoline compounds.

Original languageEnglish (US)
Pages (from-to)1121-1128
Number of pages8
JournalBiochemical and biophysical research communications
Volume347
Issue number4
DOIs
StatePublished - Sep 8 2006
Externally publishedYes

Keywords

  • Apoptosis
  • Cytokine
  • Imidazoline
  • Insulin
  • Islet of langerhans
  • MAPK
  • TUNEL labelling

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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