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Imidazoline compounds protect against interleukin 1beta-induced beta-cell apoptosis.

Zaitsev, S V; Appelskog, I B; Kapelioukh, I L; Yang, S N; Köhler, M; Efendic, S; Berggren, P O; Maarabouni, M

Authors

S V Zaitsev

I B Appelskog

I L Kapelioukh

S N Yang

M Köhler

S Efendic

P O Berggren



Contributors

Abstract

Imidazoline compounds have been considered for the treatment of type 2 diabetes. We have now investigated the effects of imidazolines on interleukin (IL)-1beta-induced beta-cell apoptosis and the signal transduction pathways involved. Inhibition of Ca2+ influx into beta-cells by D-600, a blocker of voltage-gated L-type Ca2+ channels, suppressed IL-1beta-induced apoptosis. Our data show that calcineurin, Ca2+/calmodulin-dependent serine/threonine protein phosphatase 2B, is responsible for the effect of Ca2+ on beta-cell apoptosis. We also demonstrate that IL-1beta-mediated apoptosis correlates with expression of inducible nitric oxide synthase (iNOS) and the increase in intracellular production of nitric oxide. An inhibitor of cGMP-dependent protein kinase (PKG), KT5823, suppressed IL-1beta-induced apoptosis, suggesting the involvement of a PKG-dependent pathway in the apoptotic process. One of the major findings in this study is that imidazoline compounds RX871024 and efaroxan, suggested as prototypes of a new generation of drugs against type 2 diabetes, can protect against IL-1beta-induced apoptosis in pancreatic beta-cells, possibly by their inhibition of the expression of iNOS, a key element in the IL-1beta-induced apoptotic pathway in pancreatic beta-cells. These data suggest that imidazoline compounds should be explored as a potential therapeutic agent for the treatment of both type 1 and type 2 diabetes.

Journal Article Type Article
Publication Date Feb 1, 2001
Deposit Date May 15, 2024
Journal Diabetes
Print ISSN 0012-1797
Electronic ISSN 1939-327X
Publisher American Diabetes Association
Peer Reviewed Peer Reviewed
Volume 50
Issue suppl_1
Article Number S70
DOI https://doi.org/10.2337/diabetes.50.2007.s70
Public URL https://keele-repository.worktribe.com/output/828274
Publisher URL https://diabetesjournals.org/diabetes/article/50/suppl_1/S70/11667/Imidazoline-compounds-protect-against-interleukin?searchresult=1