Abstract:
The extracellular calcium-sensing receptor (CaR) is a 7-transmembrane
spanning G-protein-coupled receptor commonly associated with the regulation of
systemic Ca2+-homeostasis. However, it is becoming increasingly apparent that
the CaR has diverse effects outside this primary role.
•In keratinocytes, inactivation of CaR expression has been shown to suppress the
assembly of the cell adhesion associated epithelial-cadherin (ECAD) and bcatenin-
PI3K complex [1]. Pancreatic β-cells express the CaR [2]. From our own
studies, pancreatic β-cells demonstrate a close association between adherens
junction proteins and secretory granules [3]. Neutralising ECAD-mediated cell
adhesion decreases glucose-evoked synchronicity in Ca2+-signals between
adjacent cells within islets [4]. Together, these findings suggest an intriguing link
between cell-cell adhesion, and CaR expression/function in pancreatic β-cells.
•In the current study, we have assessed the effect of activating the CaR via the
calcimimetic R568 on the expression of ECAD, β-catenin, L-type VDCC and
CaR itself. To determine if cell-to-cell contact, alters CaR expression and
ultimately the b-cell function., ECAD-mediated cell-cell adhesion was reduced
by immuno-neutralising ECAD. The effects on non-nutrient evoked changes in
cytosolic calcium and glucose-evoked insulin secretion were examined.
