@article{Welsh_Annerén_Lindholm_Kriz_Öberg-Welsh_2000, title={Role of Tyrosine Kinase Signaling for β-Cell Replication and Survival}, volume={105}, url={https://ujms.net/index.php/ujms/article/view/6552}, DOI={10.1517/03009734000000052}, abstractNote={<p>Diabetes mellitus is commonly considered as a disease of a scant β-cell mass that fails to respond adequately to the functional demand. Tyrosine kinases may play a role for β-cell replication, differentiation (neoformation) and survival. Transfection of β-cells with DNA constructs coding for tyrosine kinase receptors yields a ligand-dependent increase of DNA synthesis in β-cells. A PCR-based technique was adopted to assess the repertoire of tyrosine kinases expressed in fetal islet-like structures, adult islets or RINm5F cells. Several tyrosine kinase receptors, such as the VEGFR-2 (vascular endothelial growth factor receptor 2) and c-Kit, were found to be present in pancreatic duct cells. Because ducts are thought to harbor β-cell precursor cells, these receptors may play a role for the neoformation of β-cells. The Src-like tyrosine kinase mouse Gtk (previously named Bsk/Iyk) is expressed in islet cells, and was found to inhibit cell proliferation. Furthermore, it conferred decreased viability in response to cytokine exposure. Shb is a Src homology 2 domain adaptor protein which participates in tyrosine kinase signaling. Transgenic mice overexpressing Shb in β-cells exhibit an increase in the neonatal β-cell mass, an improved glucose homeostasis, but also decreased survival in response to cytokines and streptozotocin. It is concluded that tyrosine kinase signaling may generate multiple responses in β-cells, involving proliferation, survival and differentiation.</p&gt;}, number={2}, journal={Upsala Journal of Medical Sciences}, author={Welsh Michael and Annerén Cecilia and Lindholm Cecilia and Kriz Vitezslav and Öberg-Welsh Charlotte}, year={2000}, month={Jul.}, pages={7-15} }