Role of Tyrosine Kinase Signaling for β-Cell Replication and Survival

  • Michael Welsh
  • Cecilia Annerén
  • Cecilia Lindholm
  • Vitezslav Kriz
  • Charlotte Öberg-Welsh

Abstract

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.

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Published
2000-07-12
How to Cite
Welsh, M., Annerén, C., Lindholm, C., Kriz, V., & Öberg-Welsh, C. (2000). Role of Tyrosine Kinase Signaling for β-Cell Replication and Survival. Upsala Journal of Medical Sciences, 105(2), 7-15. https://doi.org/10.1517/03009734000000052
Section
Original Articles