Altered tyrosine kinase signalling has been implicated in several diseases, paving the way for the development of small-molecule TKIs (tyrosine kinase inhibitors). TKIs such as imatinib, sunitinib and dasatinib are clinically used for treating chronic myeloid leukaemia, gastrointestinal stromal tumours and other malignancies. In addition to their use as anti-cancer agents, increasing evidence points towards an anti-diabetic effect of these TKIs. Imatinib and other TKIs counteract diabetes not only in non-obese diabetic mice, but also in streptozotocin diabetic mice, db/db mice, high-fat-treated rats and humans with T2D (Type 2 diabetes). Although the mechanisms of protection need to be investigated further, the effects of imatinib and other TKIs in human T2D and the rapidly growing findings from animal models of T1D (Type 1 diabetes) and T2D are encouraging and give hope to improved treatment of human diabetes. In the present article, we review the anti-diabetic effects of TKIs which appear to involve both protection against β-cell death and improved insulin sensitivity. Considering the relatively mild side effects of TKIs, we hypothesize that TKIs could be used to treat new-onset T1D, prevent T1D in individuals at high risk of developing the disease, treat the late stages of T2D and improve the outcome of islet transplantation.
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November 09 2009
Potential utility of small tyrosine kinase inhibitors in the treatment of diabetes
Dariush Mokhtari;
1Department of Medical Cell Biology, Uppsala University, Biomedicum, P.O. Box 571, S-751 23, Uppsala, Sweden
Correspondence: Dr Dariush Mokhtari (email Dariush.Mokhtari@mcb.uu.se).
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Nils Welsh
Nils Welsh
1Department of Medical Cell Biology, Uppsala University, Biomedicum, P.O. Box 571, S-751 23, Uppsala, Sweden
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Publisher: Portland Press Ltd
Received:
June 30 2009
Revision Received:
August 19 2009
Accepted:
August 24 2009
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2010 Biochemical Society
2010
Clin Sci (Lond) (2010) 118 (4): 241–247.
Article history
Received:
June 30 2009
Revision Received:
August 19 2009
Accepted:
August 24 2009
Citation
Dariush Mokhtari, Nils Welsh; Potential utility of small tyrosine kinase inhibitors in the treatment of diabetes. Clin Sci (Lond) 1 February 2010; 118 (4): 241–247. doi: https://doi.org/10.1042/CS20090348
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