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

10 Citationer (Scopus)

Abstract

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.

OriginalsprogEngelsk
TidsskriftCellular and molecular life sciences
Vol/bind65
Udgave nummer7-8
Sider (fra-til)1248-55
Antal sider8
ISSN1420-682X
DOI
StatusUdgivet - apr. 2008
Udgivet eksterntJa

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