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

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.

Citation

Zaitsev, S. V., Appelskog, I. B., Kapelioukh, I. L., Yang, S. N., Köhler, M., Efendic, S., …Maarabouni, M. (2001). Imidazoline compounds protect against interleukin 1beta-induced beta-cell apoptosis. Diabetes, 50(suppl_1), Article S70. https://doi.org/10.2337/diabetes.50.2007.s70

• 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