|Cancer||Cell death||Cell cycle||Cytoskeleton||Exo/endocytosis||Differentiation||Division||Organelles||Signalling||Stem cells||Trafficking|
Cell Biology International (2006) 30, 10131017 (Printed in Great Britain)
Imatinib mesylate (Gleevec) protects against streptozotocin-induced diabetes and islet cell death in vitro
Robert Hägerkvista, Natalia Makeevaa, Stephen Ellimanb and Nils Welsha*
aDepartment of Medical Cell Biology, Uppsala University, Biomedicum, P.O. Box 571, Husargatan 3, S-75123 Uppsala, Sweden
bDiabetes and Metabolism Disease Area, Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA
The tyrosine kinase inhibitor imatinib mesylate (Gleevec) has been demonstrated to protect various cell types from death by inhibition of Abelson tyrosine kinase (c-Abl). The aim of the present study was to establish whether imatinib protects the insulin producing β-cell from the different apoptosis promoting agents in vitro and whether imatinib counteracts streptozotocin-induced diabetes in NMRI mice. We observe that imatinib attenuated the actions of several different death promoting substances. In addition, mice injected with streptozotocin did not develop diabetes when given imatinib. The beneficial effects of imatinib may be related to inhibition of the pro-apoptotic MAP kinase JNK. We conclude that imatinib protects against β-cell death and that this may contribute to the previously reported anti-diabetic actions of imatinib.
Key words: Imatinib, Pancreatic islet, Diabetes, JNK, Apoptosis.
*Corresponding author. Tel.: +46 18 42 12; fax: +46 18 471 40 59.
Received 22 May 2006/14 July 2006; accepted 6 August 2006doi:10.1016/j.cellbi.2006.08.006