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

I. I. Zaitseva, J. Størling, T. Mandrup-Poulsen, P. O. Berggren, S. V. Zaitsev

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

An insufficient number of insulin-producing β-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-1β, interferon- γ and tumor necrosis factor-α. 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
Pages (from-to)1248-1255
Number of pages8
JournalCellular and Molecular Life Sciences
Volume65
Issue number7-8
DOIs
StatePublished - Apr 1 2008
Externally publishedYes

Fingerprint

Imidazolines
efaroxan
JNK Mitogen-Activated Protein Kinases
Insulin-Secreting Cells
Chemical activation
Cells
Insulin
Medical problems
Caspase 1
Type 1 Diabetes Mellitus
Interleukin-1
Caspase 3
Type 2 Diabetes Mellitus
Interferons
Blood Glucose
Cause of Death
Nitric Oxide
Cell Death
Phosphotransferases
Tumor Necrosis Factor-alpha

Keywords

  • Apoptosis
  • Caspase
  • Cytokine
  • Imidazoline
  • Insulin-secreting cell
  • MAPK

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

Cite this

The imidazoline RX871024 induces death of proliferating insulin-secreting cells by activation of c-jun N-terminal kinase. / Zaitseva, I. I.; Størling, J.; Mandrup-Poulsen, T.; Berggren, P. O.; Zaitsev, S. V.

In: Cellular and Molecular Life Sciences, Vol. 65, No. 7-8, 01.04.2008, p. 1248-1255.

Research output: Contribution to journalArticle

Zaitseva, I. I. ; Størling, J. ; Mandrup-Poulsen, T. ; Berggren, P. O. ; Zaitsev, S. V. / The imidazoline RX871024 induces death of proliferating insulin-secreting cells by activation of c-jun N-terminal kinase. In: Cellular and Molecular Life Sciences. 2008 ; Vol. 65, No. 7-8. pp. 1248-1255.
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