Abstract:
In addition to its central role controlling systemic calcium homeostasis, the extracellular
calcium-sensing receptor (CaSR) can be found on multiple cell types not associated with
controlling plasma calcium. The endocrine pancreas is one such tissue, and it is apparent
that the receptor plays an important role in regulating b-cell function. During exocytosis,
divalent cations are coreleased with insulin and their concentration within the restricted
intercellular compartments of the pancreatic islet increases sufficiently to activate the
CaSR on neighboring cells. Acute and chronic activation of the receptor has multiple
effects on the b-cell, from increasing cadherin-based cell–cell adhesion to directly altering
the expression and function of various potassium and voltage-dependent calcium
channels. The promiscuous activation of multiple binding partners improves cell adhesion,
cell coupling, and cell-to-cell communication within the islet and is the basis for
the effect of the CaSR on b-cell function and improved glucose responsiveness.
