Abstract:
The extracellular calcium-sensing receptor (CaR) enables cells to detect and respond to changes in extracellular calcium. Our
previous studies have shown that the CaR is expressed by islet β-cells and that pharmacological activation of the islet CaR,
using the calcimimetic R568, results in enhanced secretion of insulin.
Epithelial (E)-cadherin (ECAD) is a trans-membrane protein whose extracellular domain forms calcium-dependent homodimers
with cadherins expressed on neighbouring cells facilitating cell-to-cell adhesion. This not only serves to increase adhesive
strength of the junction but also acts as a signalling ‘node’ for various proteins that can influence adhesiveness and/or initiate
intracellular signalling events. It is well established that a down-regulation of E-cadherin reduces insulin secretion.
We hypothesise that the extracellular calcium-sensing receptor modifies cell-to-cell adhesion within the pancreatic islet and
predict that activating the receptor increases ECAD expression and function.
