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The imidazoline RX871024 induces death of proliferating insulin-secreting cells by activation of c-jun N-terminal kinase

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  • I I Zaitseva
  • J Størling
  • T Mandrup-Poulsen
  • P-O Berggren
  • S V Zaitsev
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An insufficient number of insulin-producing beta-cells is a major cause of defective control of blood glucose in both type 1 and type 2 diabetes. The aim of this study was to clarify whether the insulinotropic imidazolines can affect the survival of highly proliferating insulin-secreting cells, here exemplified by the MIN6 cell line. Our data demonstrate that RX871024, but not efaroxan, triggered MIN6 cell death and potentiated death induced by a combination of the pro-inflammatory cytokines interleukin-1beta, interferon- gamma and tumor necrosis factor-alpha. These effects did not involve changes in nitric oxide production but correlated with stimulation of c-jun N-terminal kinase (JNK) activity and activation of caspases-1, -3, -8 and -9. Our results suggest that the imidazoline RX871024 causes death of highly proliferating insulin-secreting cells, putatively via augmentation of JNK activity, a finding that may impact on the possibility of using compounds of similar activity in the treatment of diabetes.

Original languageEnglish
JournalCellular and molecular life sciences : CMLS
Volume65
Issue number7-8
Pages (from-to)1248-55
Number of pages8
ISSN1420-682X
DOIs
Publication statusPublished - Apr 2008
Externally publishedYes

    Research areas

  • Animals, Benzofurans, Caspases, Cell Death, Cell Line, Cell Proliferation, Cytokines, Enzyme Activation, Humans, Imidazoles, Indoles, Insulin-Secreting Cells, JNK Mitogen-Activated Protein Kinases, Mice, Nitric Oxide, Journal Article, Research Support, Non-U.S. Gov't

ID: 52805689