Imatinib mesylate (Gleevec) protects against streptozotocin-induced diabetes and islet cell death in vitro.
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 beta-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 beta-cell death and that this may contribute to the previously reported anti-diabetic actions of imatinib.
Hägerkvist
Robert
R
Department of Medical Cell Biology, Uppsala University, Biomedicum, P.O. Box 571, Husargatan 3, S-75123 Uppsala, Sweden.
Makeeva
Natalia
N
Elliman
Stephen
S
Welsh
Nils
N
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D006943:Hyperglycemia / Q000517:prevention & control; D000068877:Imatinib Mesylate; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects* / Q000473:pathology; D008297:Male; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D013311:Streptozocin; D000068877:Imatinib Mesylate