Reciprocal regulation of the extracellular calcium-sensing receptor & epithelial-cadherin in pancreatic islets

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.