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.
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Received 13 December 2007; received after revision 5 February 2008; accepted 6 February 2008
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Zaitseva, I.I., Størling, J., Mandrup-Poulsen, T. et al. The imidazoline RX871024 induces death of proliferating insulin-secreting cells by activation of c-jun N-terminal kinase. Cell. Mol. Life Sci. 65, 1248–1255 (2008). https://doi.org/10.1007/s00018-008-7564-x
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DOI: https://doi.org/10.1007/s00018-008-7564-x