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Imidazoline compounds protect against interleukin 1beta-induced beta-cell apoptosis.
- Source :
-
Diabetes . Feb2001 Supplement, Vol. 50, pS70-S76. 7p. 1 Diagram, 6 Graphs. - Publication Year :
- 2001
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *IMIDAZOLINES
*CALCIUM antagonists
*ANIMAL experimentation
*APOPTOSIS
*ARGININE
*BIOLOGICAL models
*BIOLOGICAL transport
*CALCIUM
*CELL culture
*COMPARATIVE studies
*CYTOLOGY
*DOSE-effect relationship in pharmacology
*ENZYME inhibitors
*HETEROCYCLIC compounds
*HYDROLASES
*IMIDAZOLES
*IMMUNOSUPPRESSIVE agents
*INSECTICIDES
*INTERLEUKIN-1
*ISLANDS of Langerhans
*RESEARCH methodology
*MEDICAL cooperation
*MICE
*ORGANIC compounds
*OXIDOREDUCTASES
*RESEARCH
*VERAPAMIL
*EVALUATION research
*INDOLE compounds
*CHEMICAL inhibitors
*PHARMACODYNAMICS
*PHYSIOLOGY
APOPTOSIS prevention
Subjects
Details
- Language :
- English
- ISSN :
- 00121797
- Volume :
- 50
- Database :
- Academic Search Index
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 4121987
- Full Text :
- https://doi.org/10.2337/diabetes.50.2007.S70