Trends in Endocrinology & Metabolism
ReviewTyrosine Kinase Inhibitors and Diabetes: A Novel Treatment Paradigm?
Section snippets
Tyrosine Kinase Inhibitors and Diabetes: The Basics
PTKs phosphorylate tyrosine residues on target proteins, thereby changing their function. Deregulation of PTK activity, by genetic or epigenetic alterations, is implicated in various proliferative conditions, especially neoplastic diseases [1]. Activated forms of these enzymes can cause increase in tumor cell growth, induce antiapoptotic effects, and promote angiogenesis [2] (Box 1). This basic understanding has paved the way for the development of selective TKIs that attenuate these activities.
Antidiabetic Effects of TKIs
Over the past few years, several reports in the literature from clinical observations, animal models, and in vitro studies have documented the effect of TKIs in glucose metabolism in both T1DM and T2DM (Table 1, Table 2).
The Antidiabetic Effect of TKIs: Potential Mechanisms
The potential mechanisms underlying the antidiabetic action of TKI may differ depending on the type of the tyrosine kinase that is inhibited (Figure 1). However, in some of the antidiabetic effects of imatinib, there is still uncertainty regarding the molecular mechanisms involved.
Concluding Remarks and Future Perspectives
Clinical reports, as well as experimental animal and in vitro studies, have provided sufficient evidence that TKIs not only reverse, but also prevent the clinical manifestation of both T1DM and T2DM. By inhibiting several tyrosine kinases, this new class of agents exerts multiple effects that target the two main defects of diabetes: insulin resistance and β cell dysfunction.
In contrast to conventional therapy, TKIs appear to preserve β cell function, which has been regarded as the Holy Grail
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