Tyrosine Kinase Inhibitors and Diabetes: A Novel Treatment Paradigm?
Deregulation of protein tyrosine kinase (PTK) activity is implicated in various proliferative conditions. Multi-target tyrosine kinase inhibitors (TKIs) are increasingly used for the treatment of different malignancies. Recently, several clinical cases of the reversal of both type 1 and 2 diabetes mellitus (T1DM, T2DM) during TKI administration have been reported. Experimental in vivo and in vitro studies have elucidated some of the mechanisms behind this effect. For example, inhibition of Abelson tyrosine kinase (c-Abl) results in β cell survival and enhanced insulin secretion, while platelet-derived growth factor receptor (PDGFR) and epidermal growth factor receptor (EGFR) inhibition leads to improvement in insulin sensitivity. In addition, inhibition of vascular endothelial growth factor receptor 2 (VEGFR2) reduces the degree of islet cell inflammation (insulitis). Therefore, targeting several PTKs may provide a novel approach for correcting the pathophysiologic disturbances of diabetes.
Department of Endocrinology, University of Ioannina, Stavros Niarchos Avenue, 45110, Ioannina, Greece.
Athanasios
A
Fountas
Department of Endocrinology, University of Ioannina, Stavros Niarchos Avenue, 45110, Ioannina, Greece.
Leonidas-Nikolaos
LN
Diamantopoulos
Department of Endocrinology, University of Ioannina, Stavros Niarchos Avenue, 45110, Ioannina, Greece. Electronic address: atsatsou@uoi.gr.
Agathocles
A
Tsatsoulis
D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*
D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor
EGFR; PDGFR; VEGFR; c-Abl; diabetes mellitus; tyrosine kinase inhibitors